You searched for subject:(Cadherin).
Showing records 1 – 30 of
375 total matches.
◁ [1] [2] [3] [4] [5] … [13] ▶
University of Illinois – Chicago
1.
Kruse, Kevin Jonathan.
N-Cadherin Juxtacrine Signaling Regulates the Endothelial Barrier.
Degree: 2018, University of Illinois – Chicago
URL: http://hdl.handle.net/10027/23156 
► Endothelial cells express Vascular Endothelial (VE)- and Neural (N)-cadherin, which have overlapping functions. VE-cadherin forms homotypic adhesion between endothelial cells whereas N-cadherin forms heterotypic adhesion…
(more)
▼ Endothelial cells express Vascular Endothelial (VE)- and Neural (N)-
cadherin, which have overlapping functions. VE-
cadherin forms homotypic adhesion between endothelial cells whereas N-
cadherin forms heterotypic adhesion with the surrounding pericytes in capillary endothelia. Endothelial specific deletions of Cdh2 (N-
cadherin) or Cdh5 (VE-
cadherin) in mice demonstrated poorly formed leaky capillaries and in utero death at E9.5 due to defective angiogenesis. These findings raise the question of whether N- and VE-
cadherin function independently or whether N-
cadherin activated signaling regulates the assembly of VE-
cadherin and thereby the formation of adherens junctions. I investigated the role of N-
cadherin in the formation of VE-
cadherin junctions using mouse genetic models and identified N-
cadherin a novel signaling pathway in endothelial cells. I show that N-
cadherin functions by interacting with the RhoGEF Trio to activate the RhoGTPases Rac1 and RhoA at adherens junctions, inducing the recruitment of VE-
cadherin. This N-
cadherin activated signaling pathway is essential for maximal VE-
cadherin assembly and the formation of the endothelial junctional barrier.
Advisors/Committee Members: Komarova, Yulia (advisor), Mehta, Dolly (committee member), Levitan, Irena (committee member), Shin, Jae-Won (committee member), Tai, Leon (committee member), Komarova, Yulia (chair).
Subjects/Keywords: Cadherin; Endothelial
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kruse, K. J. (2018). N-Cadherin Juxtacrine Signaling Regulates the Endothelial Barrier. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/23156
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Kruse, Kevin Jonathan. “N-Cadherin Juxtacrine Signaling Regulates the Endothelial Barrier.” 2018. Thesis, University of Illinois – Chicago. Accessed April 16, 2021.
http://hdl.handle.net/10027/23156.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Kruse, Kevin Jonathan. “N-Cadherin Juxtacrine Signaling Regulates the Endothelial Barrier.” 2018. Web. 16 Apr 2021.
Vancouver:
Kruse KJ. N-Cadherin Juxtacrine Signaling Regulates the Endothelial Barrier. [Internet] [Thesis]. University of Illinois – Chicago; 2018. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/10027/23156.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Kruse KJ. N-Cadherin Juxtacrine Signaling Regulates the Endothelial Barrier. [Thesis]. University of Illinois – Chicago; 2018. Available from: http://hdl.handle.net/10027/23156
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Illinois – Urbana-Champaign
2.
Tabdili, Hamid Todd.
Mechanotransduction at cell-cell contacts.
Degree: PhD, Chemical Engineering, 2018, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/101029
► For nearly 40 years, it was debated as to whether the differences in cadherin- dependent cell-cell adhesion energies could solely predict cell sorting. Although adhesion…
(more)
▼ For nearly 40 years, it was debated as to whether the differences in
cadherin- dependent cell-cell adhesion energies could solely predict cell sorting. Although adhesion energies do influence cell sorting in vitro, recent studies suggested that that differences in cell adhesion, determined mainly by
cadherin binding affinities and expression levels, were not sufficient to predict cell sorting. This result suggested that other factors contribute. Besides their adhesive function, cadherins are also signaling proteins. Naturally, the next question is whether differences in downstream signaling associated with differences in
cadherin affinity might also contribute to cell segregation. Chapter 2 of this dissertation specifically therefore investigates the relationship between
cadherin affinities and signaling by small Rho GTPases, which are cytoskeletal regulatory proteins that influence actin polymerization and myosin dependent contractility. Recent findings also suggested that adhesion energies and cell mechanics together influence cell sorting, but the link between the two parameters had not been established. Chapter 3 builds on recent findings that
cadherin complexes are also force transducers, and addresses whether differences in
cadherin affinity also differentially alter cell mechanics. Studies discovered a significant difference between force transduction triggered by homophilic versus heterophilic
cadherin bonds that could differentially influence cell mechanics. I further investigated the mechanism of force transduction at
cadherin junctions, as described in Chapter 4 of this thesis. Chapter 4 specifically focused on the role of α-catenin—a key component in
cadherin complexes—as a critical force transducer at cell-cell adhesions
Advisors/Committee Members: Leckband, Deborah E (advisor), Leckband, Deborah E (Committee Chair), KENIS, Paul J.A (Committee Chair), RAO, Christopher V (Committee Chair), Brieher, William (Committee Chair).
Subjects/Keywords: CADHERIN; MECHANOTRANSDUCTION
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Tabdili, H. T. (2018). Mechanotransduction at cell-cell contacts. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/101029
Chicago Manual of Style (16th Edition):
Tabdili, Hamid Todd. “Mechanotransduction at cell-cell contacts.” 2018. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 16, 2021.
http://hdl.handle.net/2142/101029.
MLA Handbook (7th Edition):
Tabdili, Hamid Todd. “Mechanotransduction at cell-cell contacts.” 2018. Web. 16 Apr 2021.
Vancouver:
Tabdili HT. Mechanotransduction at cell-cell contacts. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2018. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/2142/101029.
Council of Science Editors:
Tabdili HT. Mechanotransduction at cell-cell contacts. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2018. Available from: http://hdl.handle.net/2142/101029
University of Illinois – Urbana-Champaign
3.
Shashikanth, Nitesh.
Regulation of cadherin adhesion at intercellular junctions.
Degree: PhD, Biochemistry, 2016, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/93006
► Adhesion proteins maintain cell-cell interactions, which are critical for tissue formation and the hierarchical organization of all multicellular organisms, and among them, cadherins are the…
(more)
▼ Adhesion proteins maintain cell-cell interactions, which are critical for tissue formation and the hierarchical organization of all multicellular organisms, and among them, cadherins are the major transmembrane cell-cell adhesion proteins in all vertebrate tissues. Regulation of
cadherin mediated adhesion at cell-cell junctions is crucial to our understanding of development and disease. This thesis focuses on the regulation of
cadherin adhesion, which can be influenced by its extracellular domain interactions, ligand or antibody binding, post translational modifications, or inside out signaling from cytoplasmic binding proteins.
In this thesis, micropipette-based adhesion frequency measurements of
cadherin-mediated, cell-cell binding kinetics identified a unique kinetic signature that appears to reflect both adhesive (trans) bonds between cadherins on opposing cells and lateral (cis) interactions between cadherins on the same cell. These kinetic measurements were used to assess the impact of confinement within narrow adhesion zones on the assembly of intercellular adhesions. Specifically, a unique kinetic signature suggested the formation of lateral interactions that were not detected in solution binding assays. Mutations postulated to disrupt lateral
cadherin association altered the kinetic signature, but did not affect
cadherin binding affinity. Perturbed kinetics further correlated with altered
cadherin clustering at cell-cell junctions, wound healing dynamics, and paracellular permeability.
Adhesion frequency measurements were used to demonstrate the allosteric regulation of
cadherin adhesive function. In this thesis, measured kinetics of
cadherin-mediated intercellular adhesion demonstrated quantitatively that activating anti-E-
cadherin monoclonal antibodies or the dephosphorylation of a cytoplasmic binding partner, p120 catenin, increased the homophilic binding affinity of E-
cadherin on Colo 205 cells. Further studies of Colo 205 cells demonstrated that four treatments, which similarly altered p120 catenin phosphorylation resulted in quantitatively similar enhancement in E-
cadherin affinity.
Using this approach, I further investigated the effect of N-linked and O-linked glycosylation on E-
cadherin activity and function. Results revealed that, contrary to the influence of glycosylation on N-
cadherin function, N-glycosylation of E-
cadherin in the EC4 and EC5 domains negatively regulated
cadherin adhesion, by altering binding kinetics and clustering at cell-cell junctions. This suggests the influence of N-glycosylation depends on its position in the
cadherin ectodomain.
In conclusion, this dissertation describes studies which elucidated different mechanisms regulating
cadherin adhesive function. Results showed that
cadherin binding is regulated by its ectodomain interactions at cell-cell junctions, by glycosylation, and by allosteric inside-out signaling. These findings were enabled by the adhesion frequency measurements, which enabled quantitative assessment of
cadherin binding function, in the native…
Advisors/Committee Members: Leckband, Deborah (advisor), Leckband, Deborah (Committee Chair), Martinis, Susan (committee member), Brieher, William (committee member), Tajkhorshid, Emad (committee member).
Subjects/Keywords: Cadherin; Kinetics
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Shashikanth, N. (2016). Regulation of cadherin adhesion at intercellular junctions. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/93006
Chicago Manual of Style (16th Edition):
Shashikanth, Nitesh. “Regulation of cadherin adhesion at intercellular junctions.” 2016. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 16, 2021.
http://hdl.handle.net/2142/93006.
MLA Handbook (7th Edition):
Shashikanth, Nitesh. “Regulation of cadherin adhesion at intercellular junctions.” 2016. Web. 16 Apr 2021.
Vancouver:
Shashikanth N. Regulation of cadherin adhesion at intercellular junctions. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2016. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/2142/93006.
Council of Science Editors:
Shashikanth N. Regulation of cadherin adhesion at intercellular junctions. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2016. Available from: http://hdl.handle.net/2142/93006
4.
Jungles, Jared Michael.
The Impact of pH on the Structure and Function of Neural Cadherin.
Degree: M.S. in Chemistry, Chemistry and Biochemistry, 2014, University of Mississippi
URL: https://egrove.olemiss.edu/etd/1288
► Neural (N-) cadherin is a transmembrane protein within adherens junctions that mediates cell-cell adhesion. It has 5 modular extracellular domains (EC1-EC5) that bind 3 calcium…
(more)
▼ Neural (N-)
cadherin is a transmembrane protein within adherens junctions that mediates cell-cell adhesion. It has 5 modular extracellular domains (EC1-EC5) that bind 3 calcium ions between each of the modules. Calcium binding is required for dimerization. N-
cadherin is involved in diverse processes including tissue morphogenesis, excitatory synapse formation and dynamics, and metastasis of cancer. During neurotransmission and tumorigenesis, fluctuations in extracellular pH occur, causing tissue acidosis with associated physiological consequences. Studies reported here aim to determine the effect of pH on the dimerization properties of EC1-EC2 N-
cadherin in vitro. Since N-
cadherin is an anionic protein, we hypothesized that acidification of solution would cause an increase in stability of the apo protein, a decrease in the calcium-binding affinity and a concomitant decrease in the formation of adhesive dimer. The stability of the apo monomer was increased, and the calcium-binding affinity was decreased at reduced pH, consistent with our hypothesis. Surprisingly, analytical SEC studies showed an increase in calcium-induced dimerization as solution pH decreased from 7.4 to 5.0. Salt-dependent dimerization studies indicated that electrostatic repulsion attenuates dimerization affinity. These results point to a possible electrostatic mechanism for moderating dimerization affinity of the Type I
cadherin family.
Advisors/Committee Members: Susan Pedigo, Nathan Hammer, Michael Mossing.
Subjects/Keywords: Cadherin; Electrostatics; Neural Cadherin; pH; Chemistry
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Jungles, J. M. (2014). The Impact of pH on the Structure and Function of Neural Cadherin. (Thesis). University of Mississippi. Retrieved from https://egrove.olemiss.edu/etd/1288
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Jungles, Jared Michael. “The Impact of pH on the Structure and Function of Neural Cadherin.” 2014. Thesis, University of Mississippi. Accessed April 16, 2021.
https://egrove.olemiss.edu/etd/1288.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Jungles, Jared Michael. “The Impact of pH on the Structure and Function of Neural Cadherin.” 2014. Web. 16 Apr 2021.
Vancouver:
Jungles JM. The Impact of pH on the Structure and Function of Neural Cadherin. [Internet] [Thesis]. University of Mississippi; 2014. [cited 2021 Apr 16].
Available from: https://egrove.olemiss.edu/etd/1288.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Jungles JM. The Impact of pH on the Structure and Function of Neural Cadherin. [Thesis]. University of Mississippi; 2014. Available from: https://egrove.olemiss.edu/etd/1288
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Manchester
5.
Abdalla, Zahra.
Investigation of E-cadherin expression in oral epithelial
dysplasia and squamous cell carcinoma.
Degree: 2016, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:299283
► Oral squamous cell carcinoma (OSCC) is a highly aggressive cancer that is characterized by a high rate of invasion and destruction to the surrounding tissues,…
(more)
▼ Oral squamous cell carcinoma (OSCC) is a highly
aggressive cancer that is characterized by a high rate of invasion
and destruction to the surrounding tissues, with patients showing
poor 5-year survival rate. A pre-malignant stage of cellular atypia
and loss of stratification within the epithelium (dysplasia) occurs
prior to the establishment of OSCC, which is manifested as white
(leukoplakia) or red (erythroplakia) lesions. Treatment of
dysplasia/OSCC involves surgical intervention with the removal of
an adequate safety margin. However, high grade dysplasia and OSCC
exhibit high recurrence rates. To date the only method used to
diagnose oral epithelial dysplasia (OED) and OSCC is haematoxylin
and eosin staining of biopsies and examination by an experienced
pathologist. Furthermore, the mechanisms of dysplasia formation,
transition to OSCC, and high recurrence rates are little
understood. Recent data from the Ward lab suggests that the cell
surface tumour suppressor protein E-
cadherin plays an important
role in regulating many cellular functions in epithelial cells.
Loss of E-
cadherin in carcinomas has been well studied and is
linked with tumour invasion, metastasis and poorer patient
outcomes. In this thesis, I have investigated expression of
E-
cadherin in low grade (LG) and high grade (HG) dysplasia and T1
and T4 OSCC patient biopsies to determine whether loss of this
protein occurs prior to tumour cell invasion. Furthermore,
microarray data analysis identified Epithelial Membrane Protein-1
(EMP-1) as a putative early marker of tumorigenesis, with
alterations of N-
cadherin, CD44 and 5T4 oncofoetal antigen
expression during tumorigenesis inferred from our studies in
embryonic stem cells. Immunofluorescence microscopy (IFM) analysis
revealed that normal oral epithelium exhibits cell surface
E-
cadherin, EMP-1 and 5T4 expression but generally lacks N-
cadherin
and CD44 reactivity. The statistically significant loss of both
E-
cadherin and EMP-1 was observed in low and high grade dysplastic
tissue and OSCC biopsies (p<0.001). 5T4 expression was decreased
in HG dysplasia (p<0.001), suggesting this may be a useful assay
for discriminating between LG and HG dysplastic tissues. N-
cadherin
or CD44 did not show any statistical significance in expression
between normal, LG/HG dysplasia and T1/T4 OSCC, although there was
a trend for increased N-
cadherin expression in T4 OSCC.
Significantly, E-
cadherin expression was decreased or absent from
surgical margins of LG/HG dysplasia and T1 OSCC, and EMP-1 and 5T4
were absent from the margins of LG and HG dysplastic tissue,
indicating that these margins are abnormal. Therefore, loss of
E-
cadherin and EMP-1 are early events associated with dysplastic
tissue and may be a useful method to confirm the removal of
sufficient surgical safety margin. The OSCC cell line BICR56 was
assessed for marker expression and exhibited a phenotype consistent
with normal oral epithelium. Inhibition of E-
cadherin protein in
BICR56 cells using a neutralising antibody led to decreased cell
surface localisation…
Advisors/Committee Members: MERRY, CATHERINE CLR, Merry, Catherine, Ward, Christopher.
Subjects/Keywords: E-cadherin; OSCC
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Abdalla, Z. (2016). Investigation of E-cadherin expression in oral epithelial
dysplasia and squamous cell carcinoma. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:299283
Chicago Manual of Style (16th Edition):
Abdalla, Zahra. “Investigation of E-cadherin expression in oral epithelial
dysplasia and squamous cell carcinoma.” 2016. Doctoral Dissertation, University of Manchester. Accessed April 16, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:299283.
MLA Handbook (7th Edition):
Abdalla, Zahra. “Investigation of E-cadherin expression in oral epithelial
dysplasia and squamous cell carcinoma.” 2016. Web. 16 Apr 2021.
Vancouver:
Abdalla Z. Investigation of E-cadherin expression in oral epithelial
dysplasia and squamous cell carcinoma. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2021 Apr 16].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:299283.
Council of Science Editors:
Abdalla Z. Investigation of E-cadherin expression in oral epithelial
dysplasia and squamous cell carcinoma. [Doctoral Dissertation]. University of Manchester; 2016. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:299283
Vanderbilt University
6.
Yu, Huapeng.
p120-catenin controls contractility along the vertical axis of epithelial lateral membranes.
Degree: PhD, Cancer Biology, 2015, Vanderbilt University
URL: http://hdl.handle.net/1803/15207
► In vertebrate epithelia, p120-catenin mediates E-cadherin stability and suppression of RhoA. Genetic ablation of p120 in various epithelial tissues typically causes striking alterations in tissue…
(more)
▼ In vertebrate epithelia, p120-catenin mediates E-
cadherin stability and suppression of RhoA. Genetic ablation of p120 in various epithelial tissues typically causes striking alterations in tissue function and morphology. Although these effects could very well involve p120‘s activity towards Rho, ascertaining the impact of this relationship has been complicated by the fact that p120 is also required for cell-cell adhesion. Here, we have molecularly uncoupled p120’s
cadherin stabilizing- and RhoA-suppressing activity. Unexpectedly, removing p120‘s Rho-suppressing activity dramatically disrupted the integrity of the apical surface, irrespective of E-
cadherin stability. The physical defect was tracked to excessive actomyosin contractility along the vertical axis of lateral membranes. Thus, we suggest that p120’s distinct activities toward E-
cadherin and Rho are molecularly and functionally coupled, and this in turn enables the maintenance of cell shape in the larger context of an epithelial monolayer. Importantly, local suppression of contractility by
cadherin-bound p120 appears to go beyond regulating cell shape, as loss of this activity also leads to major defects in epithelial lumenogenesis.
Advisors/Committee Members: Rebecca A. Ihrie (committee member), Albert B.Reynolds (committee member), William P. Tansey (committee member), Jonathan M. Irish (committee member), Jin Chen (Committee Chair).
Subjects/Keywords: contractility; cadherin; catenin
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Yu, H. (2015). p120-catenin controls contractility along the vertical axis of epithelial lateral membranes. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/15207
Chicago Manual of Style (16th Edition):
Yu, Huapeng. “p120-catenin controls contractility along the vertical axis of epithelial lateral membranes.” 2015. Doctoral Dissertation, Vanderbilt University. Accessed April 16, 2021.
http://hdl.handle.net/1803/15207.
MLA Handbook (7th Edition):
Yu, Huapeng. “p120-catenin controls contractility along the vertical axis of epithelial lateral membranes.” 2015. Web. 16 Apr 2021.
Vancouver:
Yu H. p120-catenin controls contractility along the vertical axis of epithelial lateral membranes. [Internet] [Doctoral dissertation]. Vanderbilt University; 2015. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/1803/15207.
Council of Science Editors:
Yu H. p120-catenin controls contractility along the vertical axis of epithelial lateral membranes. [Doctoral Dissertation]. Vanderbilt University; 2015. Available from: http://hdl.handle.net/1803/15207
University of Illinois – Urbana-Champaign
7.
Ahmed, Syeda Tajin.
Investigation of minimum fragment requirement for mimicking n-cadherin mediated adhesion.
Degree: MS, Chemical Engineering, 2018, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/102855
► Cadherins are transmembrane glycoproteins that are involved in maintaining integrity of cell junctions, morphogenesis, cell sorting and many more important biological processes. In my thesis,…
(more)
▼ Cadherins are transmembrane glycoproteins that are involved in maintaining integrity of cell junctions, morphogenesis, cell sorting and many more important biological processes. In my thesis, I have focused on studying the binding affinity of a class of
cadherin superfamily called N-cadherins. Prior studies have demonstrated that N-cadherins can promote neuronal growth and axonal regeneration in vitro. Moreover, there is a growing interest in development of small molecules targeting N-cadherins and designing of therapeutic agents to promote cell survival and axonal regeneration as well as inhibit
cadherin mediated signaling. For in vitro studies, knowing the minimum fragments of adhesive binding domain i.e. extracellular domains that can recapitulate the wild type N-
cadherin binding functions can help develop designing of biomaterials and platforms to study N-
cadherin interactions. Two dimensional affinity measurements reveal probability of stable bond formation during homophilic and/or heterophilic interactions between cadherins via extracellular domains. In order to determine the minimum fragment of the extracellular domain required for binding to mimic full length
cadherin and wild type cadherins expressed on cell surfaces, Micropipette Aspiration Assay (MPA) was performed. Using N-
cadherin as a model for classical cadherins, the binding affinity of full length N-
cadherin (N-cad EC1-5) expressed on a test cell surface (here, mesenchymal stem cell (MSCs) with the first two extracellular domains (N-cad EC1-2) and the binding pocket sequence HAVDI peptide and full length N-
cadherin (N-cad EC 1-5) were measured by this assay. The first chapter of my thesis, I talked about the structural differences of most studied cadherins E and N-cadherins and briefly described the importance of the flanking amino acid of binding pocket sequence HAVDI in N-cadherins. In the following chapter, I describe the experimental approach for determining the binding affinities of N-
cadherin fragments and compared the 2D binding affinity results with that of the full length wild type N-
cadherin expressed on MSCs. Surprisingly, the results of the study revealed that there is no significantly difference in binding affinity between N-cad EC1-2 and N-cad EC1-5 as well as HAVDI and N-cad EC1-5. The MPA studies were conducted with both wild type MSCs expressing N-cad EC1-5 as well as RBCs modified with N-cad EC1-5. However, there is a lower binding affinity between E-
cadherin and HAVDI than that between N-
cadherin and HAVDI. These results demonstrate the importance of the flanking amino acids next to HAV sequence in
cadherin specificity as well as the possible application of small peptide sequence HAVDI as a novel antagonist in processes involving N-
cadherin mediated adhesion.
Advisors/Committee Members: Leckband, Deborah E. (advisor).
Subjects/Keywords: Cadherin; binding affinity
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ahmed, S. T. (2018). Investigation of minimum fragment requirement for mimicking n-cadherin mediated adhesion. (Thesis). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/102855
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ahmed, Syeda Tajin. “Investigation of minimum fragment requirement for mimicking n-cadherin mediated adhesion.” 2018. Thesis, University of Illinois – Urbana-Champaign. Accessed April 16, 2021.
http://hdl.handle.net/2142/102855.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ahmed, Syeda Tajin. “Investigation of minimum fragment requirement for mimicking n-cadherin mediated adhesion.” 2018. Web. 16 Apr 2021.
Vancouver:
Ahmed ST. Investigation of minimum fragment requirement for mimicking n-cadherin mediated adhesion. [Internet] [Thesis]. University of Illinois – Urbana-Champaign; 2018. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/2142/102855.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ahmed ST. Investigation of minimum fragment requirement for mimicking n-cadherin mediated adhesion. [Thesis]. University of Illinois – Urbana-Champaign; 2018. Available from: http://hdl.handle.net/2142/102855
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Otago
8.
D'Costa, Zarina.
Regulation of E-cadherin by Human Papillomavirus type 16 E6
.
Degree: 2011, University of Otago
URL: http://hdl.handle.net/10523/1903
► The primary risk factor for the development of cervical cancer is a persistent infection with certain high-risk human papillomavirus (HPV) types such as 16 and…
(more)
▼ The primary risk factor for the development of cervical cancer is a persistent infection with certain high-risk human papillomavirus (HPV) types such as 16 and 18. The ability of these viruses to cause such persistent infections within the host can be attributed to several immune evasion mechanisms. One such mechanism involves adversely affecting the amount of viral antigen presented to the host immune system. It was previously shown that the E6 oncoprotein of HPV16 is capable of actively down-regulating expression of epithelial (E)-
cadherin expression which directly correlates with depletion in the number of immune Langerhans cells (LCs) in the infected tissue. In this manner, HPV16 E6 is able to contribute to viral survival and protection.
The aims of this study were firstly, to investigate the mechanism of E6 regulation of E-
cadherin; secondly, to identify a region of E6 responsible for regulation of E-
cadherin; thirdly, to investigate the roles of the other HPV16 oncoproteins in E-
cadherin regulation and fourthly, to identify potential therapeutic interventions for early HPV16 infections.
The E6 oncoprotein from HPV16 was expressed in HCT116 cells and its ability to regulate E-
cadherin promoter, transcript and surface protein was investigated. E6 was found to regulate E-
cadherin at a transcriptional level. The E-
cadherin promoter was found to be repressed in HCT116 E6 cells through a methylation dependent mechanism that is independent of direct methylation of the E-
cadherin promoter. In order to identify the region of E6 oncoprotein important for E-
cadherin regulation, a range of HPV16 E6 mutants were tested for their abilities to decrease transcription of E-
cadherin. Mutational analysis of HPV16 E6 led to the identification of residues 118-122 and the nearby R124 residue, located within the C-terminal zinc-finger binding domain to be important for transcriptional regulation of E-
cadherin by E6. In addition, the other major oncoproteins of HPV16, namely E5 and E7 were co-expressed with E6 and their abilities to regulate surface E-
cadherin were assessed. E7 was also found to be effective in decreasing surface E-
cadherin levels, and this effect was enhanced when the two oncoproteins were co-expressed in HCT116 cells. Furthermore, regulation of E-
cadherin by HPV16 oncoproteins was assessed under conditions of differentiation using a simple monolayer model of differentiation and a three-dimensional organotypic raft culture system. Lastly, in order to identify potential therapeutic interventions for early HPV16 infections, rational design was used to design peptide antagonists of E6 that could potentially interfere with E6 regulation of E-
cadherin. Despite efficient delivery of peptide inhibitors of E6 into target E6 expressing cells, no restoration of E-
cadherin levels were detected. However, another potential therapeutic compound, Indole-3-carbinol, was identified.
This research gives insight into the mechanism of transcriptional regulation of E-
cadherin by HPV16 E6. The data presented here suggest that…
Advisors/Committee Members: Hibma, Merilyn (advisor).
Subjects/Keywords: Human papillomavirus;
E-cadherin
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
D'Costa, Z. (2011). Regulation of E-cadherin by Human Papillomavirus type 16 E6
. (Doctoral Dissertation). University of Otago. Retrieved from http://hdl.handle.net/10523/1903
Chicago Manual of Style (16th Edition):
D'Costa, Zarina. “Regulation of E-cadherin by Human Papillomavirus type 16 E6
.” 2011. Doctoral Dissertation, University of Otago. Accessed April 16, 2021.
http://hdl.handle.net/10523/1903.
MLA Handbook (7th Edition):
D'Costa, Zarina. “Regulation of E-cadherin by Human Papillomavirus type 16 E6
.” 2011. Web. 16 Apr 2021.
Vancouver:
D'Costa Z. Regulation of E-cadherin by Human Papillomavirus type 16 E6
. [Internet] [Doctoral dissertation]. University of Otago; 2011. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/10523/1903.
Council of Science Editors:
D'Costa Z. Regulation of E-cadherin by Human Papillomavirus type 16 E6
. [Doctoral Dissertation]. University of Otago; 2011. Available from: http://hdl.handle.net/10523/1903
9.
Niimi, Rui.
Soluble Neural-cadherin as a novel biomarker for malignant bone and soft tissue tumors.
Degree: 博士 (医学), 2017, Mie University / 三重大学
URL: http://hdl.handle.net/10076/14235
► Background: Neural-cadherin (N-cadherin) is one of the most important molecules involved in tissue morphogenesis, wound healing, and the maintenance of tissue integrity. Recently, the cleavage…
(more)
▼ Background: Neural-cadherin (N-cadherin) is one of the most important molecules involved in tissue morphogenesis, wound healing, and the maintenance of tissue integrity. Recently, the cleavage of N-cadherin has become a focus of attention in the field of cancer biology. Cadherin and their ectodomain proteolytic shedding play important roles during cancer progression. The aims of this study are to investigate the serum soluble N-cadherin (sN-CAD) levels in patients with malignant bone and soft tissue tumors, and to evaluate the prognostic significance of the sN-CAD levels. Methods: We examined the level of serum sN-CAD using an ELISA in 80 malignant bone and soft tissue tumors (bone sarcoma, n = 23; soft tissue sarcoma, n = 50; metastatic cancer, n = 7) and 87 normal controls. The mean age of the patients was 51 years (range, 10-85 years) and the mean follow-up period was 43 months (range, 1-115 months). Results: The median serum sN-CAD level was 1,267 ng/ml (range, 135-2,860 ng/ml) in all patients. The mean serum sN-CAD level was 1,269 ng/ml (range, 360-2,860 ng/ml) in sarcoma patients, otherwise 1,246 ng/ml (range, 135-2,140 ng/ml) in cancer patients. The sN-CAD levels in patient were higher than those found in the controls, who had a median serum level of 108 ng/ml (range, 0-540 ng/ml). The patients with tumors larger than 5 cm had higher serum sN-CAD levels than the patients with tumors smaller than 5 cm. The histological grade in the patients with higher serum sN-CAD levels was higher than that in the patients with lower serum sN-CAD levels. A univariate analysis demonstrated that the patients with higher serum sN-CAD levels showed a worse disease-free survival rate, local recurrence-free survival rate, metastasis-free survival rate, and overall survival rate compared to those with lower serum sN-CAD levels. In the multivariate analysis, sN-CAD was an independent factor predicting disease-free survival. Conclusions: sN-CAD is a biomarker for malignant bone and soft tissue tumors, and a potentially valuable pre-therapeutic prognostic factor in patients with bone and soft tissue sarcoma.
本文 / Department of Orthopaedic Surgery, Mie University Graduate School ofMedicine
10
Subjects/Keywords: Sarcoma; Cadherin; Prognosis; Shedding; Biomarker
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Niimi, R. (2017). Soluble Neural-cadherin as a novel biomarker for malignant bone and soft tissue tumors. (Thesis). Mie University / 三重大学. Retrieved from http://hdl.handle.net/10076/14235
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Niimi, Rui. “Soluble Neural-cadherin as a novel biomarker for malignant bone and soft tissue tumors.” 2017. Thesis, Mie University / 三重大学. Accessed April 16, 2021.
http://hdl.handle.net/10076/14235.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Niimi, Rui. “Soluble Neural-cadherin as a novel biomarker for malignant bone and soft tissue tumors.” 2017. Web. 16 Apr 2021.
Vancouver:
Niimi R. Soluble Neural-cadherin as a novel biomarker for malignant bone and soft tissue tumors. [Internet] [Thesis]. Mie University / 三重大学; 2017. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/10076/14235.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Niimi R. Soluble Neural-cadherin as a novel biomarker for malignant bone and soft tissue tumors. [Thesis]. Mie University / 三重大学; 2017. Available from: http://hdl.handle.net/10076/14235
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Manchester
10.
Abdalla, Zahra Youssef.
Investigation of E-cadherin expression in oral epithelial dysplasia and squamous cell carcinoma.
Degree: PhD, 2016, University of Manchester
URL: https://www.research.manchester.ac.uk/portal/en/theses/investigation-of-ecadherin-expression-in-oral-epithelial-dysplasia-and-squamous-cell-carcinoma(8ad27ead-06f2-48e0-9a84-2ca12ea47f53).html
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740279
► Oral squamous cell carcinoma (OSCC) is a highly aggressive cancer that is characterized by a high rate of invasion and destruction to the surrounding tissues,…
(more)
▼ Oral squamous cell carcinoma (OSCC) is a highly aggressive cancer that is characterized by a high rate of invasion and destruction to the surrounding tissues, with patients showing poor 5-year survival rate. A pre-malignant stage of cellular atypia and loss of stratification within the epithelium (dysplasia) occurs prior to the establishment of OSCC, which is manifested as white (leukoplakia) or red (erythroplakia) lesions. Treatment of dysplasia/OSCC involves surgical intervention with the removal of an adequate safety margin. However, high grade dysplasia and OSCC exhibit high recurrence rates. To date the only method used to diagnose oral epithelial dysplasia (OED) and OSCC is haematoxylin and eosin staining of biopsies and examination by an experienced pathologist. Furthermore, the mechanisms of dysplasia formation, transition to OSCC, and high recurrence rates are little understood. Recent data from the Ward lab suggests that the cell surface tumour suppressor protein E-cadherin plays an important role in regulating many cellular functions in epithelial cells. Loss of E-cadherin in carcinomas has been well studied and is linked with tumour invasion, metastasis and poorer patient outcomes. In this thesis, I have investigated expression of E-cadherin in low grade (LG) and high grade (HG) dysplasia and T1 and T4 OSCC patient biopsies to determine whether loss of this protein occurs prior to tumour cell invasion. Furthermore, microarray data analysis identified Epithelial Membrane Protein-1 (EMP-1) as a putative early marker of tumorigenesis, with alterations of N-cadherin, CD44 and 5T4 oncofoetal antigen expression during tumorigenesis inferred from our studies in embryonic stem cells. Immunofluorescence microscopy (IFM) analysis revealed that normal oral epithelium exhibits cell surface E-cadherin, EMP-1 and 5T4 expression but generally lacks N-cadherin and CD44 reactivity. The statistically significant loss of both E-cadherin and EMP-1 was observed in low and high grade dysplastic tissue and OSCC biopsies (p < 0.001). 5T4 expression was decreased in HG dysplasia (p < 0.001), suggesting this may be a useful assay for discriminating between LG and HG dysplastic tissues. N-cadherin or CD44 did not show any statistical significance in expression between normal, LG/HG dysplasia and T1/T4 OSCC, although there was a trend for increased N-cadherin expression in T4 OSCC. Significantly, Ecadherin expression was decreased or absent from surgical margins of LG/HG dysplasia and T1 OSCC, and EMP-1 and 5T4 were absent from the margins of LG and HG dysplastic tissue, indicating that these margins are abnormal. Therefore, loss of Ecadherin and EMP-1 are early events associated with dysplastic tissue and may be a useful method to confirm the removal of sufficient surgical safety margin. The OSCC cell line BICR56 was assessed for marker expression and exhibited a phenotype consistent with normal oral epithelium. Inhibition of E-cadherin protein in BICR56 cells using a neutralising antibody led to decreased cell surface localisation…
Subjects/Keywords: 616.99; E-cadherin; OSCC
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Abdalla, Z. Y. (2016). Investigation of E-cadherin expression in oral epithelial dysplasia and squamous cell carcinoma. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/investigation-of-ecadherin-expression-in-oral-epithelial-dysplasia-and-squamous-cell-carcinoma(8ad27ead-06f2-48e0-9a84-2ca12ea47f53).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740279
Chicago Manual of Style (16th Edition):
Abdalla, Zahra Youssef. “Investigation of E-cadherin expression in oral epithelial dysplasia and squamous cell carcinoma.” 2016. Doctoral Dissertation, University of Manchester. Accessed April 16, 2021.
https://www.research.manchester.ac.uk/portal/en/theses/investigation-of-ecadherin-expression-in-oral-epithelial-dysplasia-and-squamous-cell-carcinoma(8ad27ead-06f2-48e0-9a84-2ca12ea47f53).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740279.
MLA Handbook (7th Edition):
Abdalla, Zahra Youssef. “Investigation of E-cadherin expression in oral epithelial dysplasia and squamous cell carcinoma.” 2016. Web. 16 Apr 2021.
Vancouver:
Abdalla ZY. Investigation of E-cadherin expression in oral epithelial dysplasia and squamous cell carcinoma. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2021 Apr 16].
Available from: https://www.research.manchester.ac.uk/portal/en/theses/investigation-of-ecadherin-expression-in-oral-epithelial-dysplasia-and-squamous-cell-carcinoma(8ad27ead-06f2-48e0-9a84-2ca12ea47f53).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740279.
Council of Science Editors:
Abdalla ZY. Investigation of E-cadherin expression in oral epithelial dysplasia and squamous cell carcinoma. [Doctoral Dissertation]. University of Manchester; 2016. Available from: https://www.research.manchester.ac.uk/portal/en/theses/investigation-of-ecadherin-expression-in-oral-epithelial-dysplasia-and-squamous-cell-carcinoma(8ad27ead-06f2-48e0-9a84-2ca12ea47f53).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740279
University of Notre Dame
11.
Oscar Pellon-Cardenas.
Regulation of Canonical Wnt Signaling in
Epithelia</h1>.
Degree: Biological Sciences, 2012, University of Notre Dame
URL: https://curate.nd.edu/show/j3860576970
► The canonical Wnt/ÌÄå_Ìâå_-catenin signaling is involved in the remodeling of epithelial tissue during early embryonic development. An essential component of the canonical Wnt pathway…
(more)
▼ The canonical Wnt/ÌÄå_Ìâå_-catenin signaling
is involved in the remodeling of epithelial tissue during early
embryonic development. An essential component of the canonical Wnt
pathway is ÌÄå_Ìâå_-catenin, whose dual role in the cell allows it
to function either as a bridge between cadherins and the actin
cytoskeleton at the adherens junctions, or as a transcriptional
transactivator of Wnt target genes when bound to lymphoid enhancer
factor (LEF)/ T-cell factor (TCF) family of transcription factors.
The dual function ÌÄå_Ìâå_-catenin in cell adhesion and
transcription is tightly regulated in vertebrates in order to
maintain a balanced level of canonical Wnt signaling. Deregulation
of this conserved developmental pathway is frequently associated
with disease, especially in pre-malignant lesions and metastatic
disease. In this research dissertation, a novel role for the ARF6
GTPase in the regulation of Wnt/ÌÄå_Ìâå_-catenin signaling via its
effect on the turnover of adhesion molecules in Madin-Darby canine
kidney (MDCK) epithelial cells, is demonstrated.
Activation of ARF6 during canonical Wnt signaling led to
intracellular accumulation of pools of active ÌÄå_Ìâå_-catenin by
promoting E-
cadherin endocytosis and triggering an intracellular
ERK-CK2 signaling cascade that results in the dissociation of
ÌÄå_Ìâå_-catenin from ÌÄå_Ìâå±-catenin complexes. The contribution
of membrane bound ÌÄå_Ìâå_-catenin to transcription initiation was
based on the presence of N-terminally dephosphorylated
ÌÄå_Ìâå_-catenin, which has been shown to mediate ÌÄå_Ìâå_-catenin
transactivation. Furthermore, ERK phosphorylates LRP6 to amplify
the Wnt transduction pathway.
Wnt/ÌÄå_Ìâå_-catenin signaling also initiated a
proliferation response that correlated with the luminal filling of
epithelial glandular structures. Sustained proliferation of cells
may be facilitated by ARF6-dependent endocytosis of the LRP6
receptor and ERK kinase. Furthermore, we showed that the ERK-CK2
signaling cascade mediates the proliferation response that sustains
luminal filling in cysts and acinar structures. Finally, the
identification of consensus sites for interaction with
transcription factors regulated by Wnt in the ARF6 promoter is
indicative of potential transcriptional control by signaling
pathways that contribute to epithelial-mesenchymal transitions. In
summary, this study identifies ARF6 as a new target of
Wnt/ÌÄå_Ìâå_-catenin activation with a therapeutic potential in
pre-invasive lesions of glandular epithelial tissue.
Advisors/Committee Members: Paul Huber, Committee Member, Joseph OTousa, Committee Member, Jeff S. Schorey, Committee Member, Crislyn DSouza Schorey, Committee Chair.
Subjects/Keywords: ARF; cadherin; Wnt; adherens junctions
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Pellon-Cardenas, O. (2012). Regulation of Canonical Wnt Signaling in
Epithelia</h1>. (Thesis). University of Notre Dame. Retrieved from https://curate.nd.edu/show/j3860576970
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Pellon-Cardenas, Oscar. “Regulation of Canonical Wnt Signaling in
Epithelia</h1>.” 2012. Thesis, University of Notre Dame. Accessed April 16, 2021.
https://curate.nd.edu/show/j3860576970.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Pellon-Cardenas, Oscar. “Regulation of Canonical Wnt Signaling in
Epithelia</h1>.” 2012. Web. 16 Apr 2021.
Vancouver:
Pellon-Cardenas O. Regulation of Canonical Wnt Signaling in
Epithelia</h1>. [Internet] [Thesis]. University of Notre Dame; 2012. [cited 2021 Apr 16].
Available from: https://curate.nd.edu/show/j3860576970.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Pellon-Cardenas O. Regulation of Canonical Wnt Signaling in
Epithelia</h1>. [Thesis]. University of Notre Dame; 2012. Available from: https://curate.nd.edu/show/j3860576970
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Queens University
12.
D'Abreo, Carmeline.
The Role of Cadherin-11 and gp130 in Transformation by Activated Src
.
Degree: Pathology and Molecular Medicine, 2011, Queens University
URL: http://hdl.handle.net/1974/6887
► Signal Transducer and Activator of Transcription 3, Stat3, has been associated with cytokine-induced proliferation, anti-apoptosis and neoplastic transformation, while constitutively active Stat3 has been found…
(more)
▼ Signal Transducer and Activator of Transcription 3, Stat3, has been associated with cytokine-induced proliferation, anti-apoptosis and neoplastic transformation, while constitutively active Stat3 has been found in many human tumors. Stat3 activation by the Src oncoprotein leads to specific gene regulation and the Stat3 mediated signaling pathway is one of the critical signaling pathways involved in Src oncogenesis. Our laboratory demonstrated that engagement of cadherins, which are a class of cell-cell adhesion molecules, can activate Stat3, even in the absence of direct cell to cell contact. Interestingly, a significant increase in total Rac1 and Cdc42 protein levels triggered by cadherin engagement, and an increase in Rac1 and Cdc42 activity, which led to Stat3 activation by a mechanism involving gp130, a common subunit of the IL-6 family of cytokines, was also observed. To investigate the role of gp130 in vSrc transformation, we knocked down gp130 in vSrc transformed cells and found a decrease in the levels of phosphorylated Stat3, the rate of cell migration, rate of cell proliferation and the anchorage-independent growth.
It was also previously demonstrated that vSrc had a negative effect on the function of cadherins. Surprisingly, however, despite the fact that vSrc may reduce cadherin adhesion, previous results in our lab showed that cell density still caused a significant increase in Stat3 activity in vSrc transformed cells. Moreover, Stat3 downregulation induced apoptosis in transformed cells which was more pronounced at high cell densities. This may reflect an increased need for Stat3 activity at high densities, possibly to overcome apoptosis, which raised the question of the actual role of cadherins in the density-mediated activation of Stat3 in such cells.
The expression of cadherin-11, a type II cell adhesion molecule, is associated with invasive breast cancer and many studies suggest that it may play a significant role in facilitating tumor cell invasion and the formation of metastatic tumors. Since Src and its family members participate in many aspects of tumor progression and metastasis, it was interesting to see if Src needed cadherin-11 for neoplastic transformation. To this effect, when we knocked down cadherin-11 in Balb/c3T3 cells, we observed a significant reduction in levels of phosphorylated Stat3-ptyr705 which was also observed when vSrc was expressed in them. Moreover, expressing vSrc in cells in which cadherin-11 was knocked down also decreased the anchorage –independent growth and increased apoptosis indicating that cadherin-11 is needed for transformation and survival respectively, in vSrc transformed cells.
Our results thus demonstrate that cadherin-11 may be a good target for the selective elimination of cells expressing Src and presumably other oncogenes as well. Stat3 activation by cadherins is so potent and important that tumor cell death can be enhanced by cadherin inhibition. In our experiments, the inhibition of cadherin-11 induced apoptosis in Src expressing…
Subjects/Keywords: Cadherin-11; Src; gp130; Stat3
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
D'Abreo, C. (2011). The Role of Cadherin-11 and gp130 in Transformation by Activated Src
. (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/6887
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
D'Abreo, Carmeline. “The Role of Cadherin-11 and gp130 in Transformation by Activated Src
.” 2011. Thesis, Queens University. Accessed April 16, 2021.
http://hdl.handle.net/1974/6887.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
D'Abreo, Carmeline. “The Role of Cadherin-11 and gp130 in Transformation by Activated Src
.” 2011. Web. 16 Apr 2021.
Vancouver:
D'Abreo C. The Role of Cadherin-11 and gp130 in Transformation by Activated Src
. [Internet] [Thesis]. Queens University; 2011. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/1974/6887.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
D'Abreo C. The Role of Cadherin-11 and gp130 in Transformation by Activated Src
. [Thesis]. Queens University; 2011. Available from: http://hdl.handle.net/1974/6887
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of British Columbia
13.
Chen, Juelei.
Twist regulates E-cadherin and N-cadherin expression levels in distinct human trophoblastic cell lines in vitro.
Degree: MS- MSc, Reproductive and Developmental Sciences, 2009, University of British Columbia
URL: http://hdl.handle.net/2429/2781
► Cadherin gene family members are known to be involved in the differentiation of cytotrophoblasts of the human placenta. In particular, the regulation of cadherin expression…
(more)
▼ Cadherin gene family members are known to be involved in the differentiation of cytotrophoblasts of the human placenta. In particular, the regulation of cadherin expression is coupled with the development of an invasive phenotype and the formation of the multinucleated syncytiotrophoblast. To investigate further the mechanisms underlying the differential regulation of cadherins during these developmental processes, we have examined the role of the transcription factor known as Twist. Twist is a basic HLH (helix-loop-helix) factor which has been shown to regulate cadherin expression in a variety of human tissues under normal and pathological conditions. Using an siRNA strategy, I have determined that Twist regulates both E-cadherin and N-cadherin in distinct subtypes of human trophoblastic cells in vitro. In particular, suppression of Twist gene expression in poorly invasive BeWo choriocarcinoma cells by using Twist-specific siRNA resulted in a concomitant increase in E-cadherin mRNA and protein levels in these cells. In contrast, transfection of highly invasive extravillous cytotrophoblasts with Twist siRNA decreased N-cadherin mRNA levels in a concentration-dependent manner. Taken together, these observations indicate that Twist differentially regulates E-cadherin and N-cadherin in human trophoblastic cells, two cadherin subtypes that govern the differentiation of these cells along the non-invasive and invasive pathways respectively. Although, the results of my studies do not directly demonstrate this biological function of Twist, they support the speculation that alterations in Twist expression levels will result in cadherin-mediated disorders of pregnancy associated with aberrant trophoblast differentiation.
Subjects/Keywords: Twist; Cadherin
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chen, J. (2009). Twist regulates E-cadherin and N-cadherin expression levels in distinct human trophoblastic cell lines in vitro. (Masters Thesis). University of British Columbia. Retrieved from http://hdl.handle.net/2429/2781
Chicago Manual of Style (16th Edition):
Chen, Juelei. “Twist regulates E-cadherin and N-cadherin expression levels in distinct human trophoblastic cell lines in vitro.” 2009. Masters Thesis, University of British Columbia. Accessed April 16, 2021.
http://hdl.handle.net/2429/2781.
MLA Handbook (7th Edition):
Chen, Juelei. “Twist regulates E-cadherin and N-cadherin expression levels in distinct human trophoblastic cell lines in vitro.” 2009. Web. 16 Apr 2021.
Vancouver:
Chen J. Twist regulates E-cadherin and N-cadherin expression levels in distinct human trophoblastic cell lines in vitro. [Internet] [Masters thesis]. University of British Columbia; 2009. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/2429/2781.
Council of Science Editors:
Chen J. Twist regulates E-cadherin and N-cadherin expression levels in distinct human trophoblastic cell lines in vitro. [Masters Thesis]. University of British Columbia; 2009. Available from: http://hdl.handle.net/2429/2781
Universiteit Utrecht
14.
Pilzecker, B.
The E- and N-cadherin switch in Epithelial to Mesenchymal Transition and metastasis.
Potential drug targets?.
Degree: 2013, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/287101
► Carcinomas are most prevalent type of cancers and arise from an epithelial layer. Epithelial layers have a strict organization; cells are tightly linked through different…
(more)
▼ Carcinomas are most prevalent type of cancers and arise from an epithelial layer. Epithelial layers have a strict organization; cells are tightly linked through different junctions. The Epithelial to Mesenchymal Transition (EMT) developmental program enables epithelial cells to transform into mesenchymal cells and break free from neighboring epithelial cells in order to migrate though the body. Also in carcinomas, EMT enables cells to invade into healthy tissue. EMT also aids cancer progression in other manners by suppressing senescence, anoikis, apoptosis, oncogene addiction and modulating the immune response. Furthermore, EMT can lead to the formation of mesenchymal cancer stem cells. Mesenchymal cancer stem cells seem to be more resistant to chemotherapy than epithelial cancer cells. All of these traits increase the chance of an invading cancer cell being successful in setting up a metastatic niche. The
cadherin switch from E-
cadherin to N-
cadherin is considered a mark of EMT. Cadherins are cell-cell adhesion proteins. E-
cadherin inhibits invasion by protecting epithelial integrity and N-
cadherin increases invasion. It seems that a part of carcinomas has an E- to N-
cadherin switch during EMT. However, other carcinomas show other
cadherin switches and E- and N-
cadherin expression is not always mutually exclusive. In the HMLE cancer cell line E-
cadherin knockdown is enough to induce EMT. By knocking out E-
cadherin and p53 in a tissue specific manner they show an increase of invasion and metastases. In gastric carcinoma model E-
cadherin and p53 knockout leads to EMT, however, in an invasive lobular carcinoma model EMT has not been observed. If EMT could be inhibited in carcinomas, the chance of metastasis would decrease and the formation of new cancer stem cells would be inhibited. Since chemotherapy mainly targets epithelial cancer cells, combining an EMT inhibitor might lead to more efficient chemotherapy. There are some compounds capable of inhibiting EMT or promoting the reverse process Mesenchymal to Epithelial Transition (MET). The identified compounds either inhibit a pathway which induces EMT or lead regaining epithelial identity and re-expression of E-
cadherin. These compounds need to be further tested using in vivo models. Antibodies targeting mesenchymal marker proteins are being developed as well. An anti N-
cadherin antibody shows a decrease of tumor growth and metastases in mice, perhaps by targeting mesenchymal cancer stem cells. Since chemotherapy does not efficiently target cancer stem cells, screens were performed to find compounds that target cancer stem cells. In the future, there may be a combined anticancer therapy developed which inhibits EMT and targets cancer stem cells. This type of therapy could be combined with chemo-, radiotherapy or surgery to treat carcinomas more efficiently.
Advisors/Committee Members: Bos, Prof. Dr. J.L..
Subjects/Keywords: Carcinomas; Epithelial to Mesenchymal Transition (EMT); E-cadherin; N-cadherin
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Pilzecker, B. (2013). The E- and N-cadherin switch in Epithelial to Mesenchymal Transition and metastasis.
Potential drug targets?. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/287101
Chicago Manual of Style (16th Edition):
Pilzecker, B. “The E- and N-cadherin switch in Epithelial to Mesenchymal Transition and metastasis.
Potential drug targets?.” 2013. Masters Thesis, Universiteit Utrecht. Accessed April 16, 2021.
http://dspace.library.uu.nl:8080/handle/1874/287101.
MLA Handbook (7th Edition):
Pilzecker, B. “The E- and N-cadherin switch in Epithelial to Mesenchymal Transition and metastasis.
Potential drug targets?.” 2013. Web. 16 Apr 2021.
Vancouver:
Pilzecker B. The E- and N-cadherin switch in Epithelial to Mesenchymal Transition and metastasis.
Potential drug targets?. [Internet] [Masters thesis]. Universiteit Utrecht; 2013. [cited 2021 Apr 16].
Available from: http://dspace.library.uu.nl:8080/handle/1874/287101.
Council of Science Editors:
Pilzecker B. The E- and N-cadherin switch in Epithelial to Mesenchymal Transition and metastasis.
Potential drug targets?. [Masters Thesis]. Universiteit Utrecht; 2013. Available from: http://dspace.library.uu.nl:8080/handle/1874/287101
15.
Nore, Andrea Marie.
Regulation Of Vectorial Active Transport In Human Proximal Tubule Cells By MT-3: The Role Of The C-Terminal Domain On E-And N-Cadherin Expression And The Confirmation Of Protein-Protein Interactions.
Degree: PhD, Biomedical Sciences, 2015, University of North Dakota
URL: https://commons.und.edu/theses/1938
► The proximal tubule of the kidney is particularly susceptible to toxicant-induced damage and cell cultures of human proximal tubule cells are widely utilized to…
(more)
▼ The proximal tubule of the kidney is particularly susceptible to toxicant-induced damage and cell cultures of human proximal tubule cells are widely utilized to study the role of epithelial-mesenchymal transition (EMT) in renal disease. Cadmium is a toxic metal ion that is known to produce renal tubular necrosis and accumulate in the proximal tubule. This metal binds to a family of cysteine rich metal binding proteins known as metallothioneins (MT) that are found in abundance in the kidney. Previous studies from our laboratory have shown that the third isoform of metallothionein (MT-3) is expressed in the epithelial cells of the human kidney, including those of the proximal tubule. An immortalized proximal tubule cell line does not express MT-3 and does not demonstrate vectorial active transport. Transfection of the MT-3 gene into the HK-2 cells restores vectorial active transport as evidenced by dome formation. This suggests that MT-3 is involved in mesenchymal to epithelial transition (MET), the reverse of EMT, and promotes and epithelial phenotype. The goals of the present study were to examine the role of growth media composition on classic EMT responses, quantitatively evaluate the expression levels of E- and N-
cadherin, define the functional epitope of MT-3 that mediates MET in HK-2 cells, and identify proteins that interact with MT-3 to promote epithelial features in the proximal tubule. It was shown that both E- and N-
cadherin mRNA and protein are expressed in the human renal proximal tubule. Based on the pattern of
cadherin expression, vectorial active transport, and transepithelial resistance, it seems that the HK-2 cell line has already undergone many of the early features associated with EMT. Our data indicates the unique, six amino acid C-terminal sequence of MT-3 is required to induce MET in HK-2 cells. A combination of co-immunoprecipitation and western blotting indicate that MT-3 interacts with myosin-IIa, β-actin, enolase-1, tropomyosin-3, and aldolase-a in vitro. Together, the data suggests the HK-2 cell line can be an effective model to study later stages in the conversion of the renal epithelial cell to a mesenchymal cell and when transfected with MT-3 it may be an effective model to study the process of MET. MT-3 protein-protein interactions provide insight into the potential mechanism by which MT-3 promotes cytoskeletal organization in non-diseased epithelial proximal tubule cells and offers the opportunity to investigate these interactions under pathological conditions.
Advisors/Committee Members: Scott H. Garrett.
Subjects/Keywords: Cadmium; E-cadherin; Kidney Disease; MT-3; N-cadherin; Proximal Tubule
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Nore, A. M. (2015). Regulation Of Vectorial Active Transport In Human Proximal Tubule Cells By MT-3: The Role Of The C-Terminal Domain On E-And N-Cadherin Expression And The Confirmation Of Protein-Protein Interactions. (Doctoral Dissertation). University of North Dakota. Retrieved from https://commons.und.edu/theses/1938
Chicago Manual of Style (16th Edition):
Nore, Andrea Marie. “Regulation Of Vectorial Active Transport In Human Proximal Tubule Cells By MT-3: The Role Of The C-Terminal Domain On E-And N-Cadherin Expression And The Confirmation Of Protein-Protein Interactions.” 2015. Doctoral Dissertation, University of North Dakota. Accessed April 16, 2021.
https://commons.und.edu/theses/1938.
MLA Handbook (7th Edition):
Nore, Andrea Marie. “Regulation Of Vectorial Active Transport In Human Proximal Tubule Cells By MT-3: The Role Of The C-Terminal Domain On E-And N-Cadherin Expression And The Confirmation Of Protein-Protein Interactions.” 2015. Web. 16 Apr 2021.
Vancouver:
Nore AM. Regulation Of Vectorial Active Transport In Human Proximal Tubule Cells By MT-3: The Role Of The C-Terminal Domain On E-And N-Cadherin Expression And The Confirmation Of Protein-Protein Interactions. [Internet] [Doctoral dissertation]. University of North Dakota; 2015. [cited 2021 Apr 16].
Available from: https://commons.und.edu/theses/1938.
Council of Science Editors:
Nore AM. Regulation Of Vectorial Active Transport In Human Proximal Tubule Cells By MT-3: The Role Of The C-Terminal Domain On E-And N-Cadherin Expression And The Confirmation Of Protein-Protein Interactions. [Doctoral Dissertation]. University of North Dakota; 2015. Available from: https://commons.und.edu/theses/1938
University of Newcastle
16.
Sadeqzadeh, Elham.
Analysis of post-translational modifications of Fat1 cadherin.
Degree: PhD, 2014, University of Newcastle
URL: http://hdl.handle.net/1959.13/1050575
► Research Doctorate - Doctor of Philoshphy (PhD)
First identified in Drosophila as a tumour-suppressor gene, Fat cadherin (Ft) and the closely related Fat2 (Ft2) have…
(more)
▼ Research Doctorate - Doctor of Philoshphy (PhD)
First identified in Drosophila as a tumour-suppressor gene, Fat cadherin (Ft) and the closely related Fat2 (Ft2) have been identified as giant members of the cadherin superfamily. Ft engages the Hippo signalling pathway during development and both receptors have been shown to function in different aspects of cell polarity and migration. There are four vertebrate homologues, Fat1-Fat4, all closely-related in structure to Drosophila ft and ft2. Over the past decade knock-out mouse studies, genetic manipulation and large sequencing projects have aided our understanding of the function of vertebrate Fat cadherins in tissue development and disease. The majority of studies of this family have focused on Fat1, with evidence now showing it can bind to ENA/VASP, β-catenin and Atrophin proteins to influence cell polarity and motility; Homer1 and 3 proteins to regulate actin accumulation in neuronal synapses; and Scribble to influence the Hippo signalling pathway. Fat2 and Fat3 can regulate cell migration in a tissue specific manner and Fat4 appears to influence both planar cell polarity and Hippo signalling recapitulating the activity of Drosophila Ft. Knowledge about the exact downstream signalling pathways activated by each family member remains in its infancy, but it is becoming clearer that each may have tissue specific and redundant roles in development. Importantly there is also evidence building to suggest that Fat cadherins may be lost or gained in certain cancers. This thesis represents the first in-depth biochemical investigation of human FAT1 cadherin, particularly its comparative expression in normal versus cancer cells. The first chapter studied the expression profile of all FAT cadherins in a panel of 20 cultured melanoma cells where all melanoma cell lines variably, but universally express FAT1 at the mRNA level and less commonly Fat2, Fat3 and Fat4. Both normal melanocytes and keratinocytes also express comparable FAT1 mRNA levels relative to melanoma cells. Analysis of the protein processing of FAT1 in keratinocytes revealed that human FAT1 was site-1 (S1) cleaved into a non-covalent heterodimer before achieving cell surface expression. A similar processing event had been reported in Drosophila Ft indicating that this was an evolutionary conserved mechanism. The use of inhibitors also established such cleavage is catalysed by a member of the proprotein convertase family, likely furin. However, in melanoma cells the non-cleaved pro-form of FAT1 was also expressed on the cell surface together with the S1-cleaved heterodimer. The appearance of both processed and non-processed forms of FAT1 on the cell surface demarked two possible biosynthetic pathways. Moreover FAT1 processing in melanoma cells generated a potentially functional proteolytic product in melanoma cells: a persistent 65kDa membrane-bound cytoplasmic fragment no longer in association with the extracellular fragment. Localisation studies of FAT1 both in vitro and in vivo showed melanoma cells display…
Advisors/Committee Members: University of Newcastle. Faculty of Health & Medicine, School of Biomedical Sciences and Pharmacy.
Subjects/Keywords: Fat cadherin; Drosophilia; cancer; cell biology
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sadeqzadeh, E. (2014). Analysis of post-translational modifications of Fat1 cadherin. (Doctoral Dissertation). University of Newcastle. Retrieved from http://hdl.handle.net/1959.13/1050575
Chicago Manual of Style (16th Edition):
Sadeqzadeh, Elham. “Analysis of post-translational modifications of Fat1 cadherin.” 2014. Doctoral Dissertation, University of Newcastle. Accessed April 16, 2021.
http://hdl.handle.net/1959.13/1050575.
MLA Handbook (7th Edition):
Sadeqzadeh, Elham. “Analysis of post-translational modifications of Fat1 cadherin.” 2014. Web. 16 Apr 2021.
Vancouver:
Sadeqzadeh E. Analysis of post-translational modifications of Fat1 cadherin. [Internet] [Doctoral dissertation]. University of Newcastle; 2014. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/1959.13/1050575.
Council of Science Editors:
Sadeqzadeh E. Analysis of post-translational modifications of Fat1 cadherin. [Doctoral Dissertation]. University of Newcastle; 2014. Available from: http://hdl.handle.net/1959.13/1050575
Vanderbilt University
17.
Smith, Andrew Leslie.
ReCLIP (Reversible Cross-Link Immuno-Precipitation) reveals a novel interaction between p120-catenin and p160 Rho Kinase.
Degree: PhD, Cancer Biology, 2011, Vanderbilt University
URL: http://hdl.handle.net/1803/11028
► p120 catenin (p120) binds and stabilizes classical cadherins, making it a critical regulator of cell-cell adhesion. Here, we report an efficient technique (designated ReCLIP for…
(more)
▼ p120 catenin (p120) binds and stabilizes classical cadherins, making it a critical regulator of cell-cell adhesion. Here, we report an efficient technique (designated ReCLIP for Reversible Cross-Link Immuno-Precipitation) for identifying novel p120 binding partners that provides evidence of an interaction between p120 and the RhoA substrate p160 Rho Kinase (ROCK1). Briefly, proteins are covalently crosslinked in situ using thiol-cleavable DSP (Dithiobis[succinimidyl propionate) or DTME (Dithio-bismaleimidoethane) chemistries and then recovered by immunoprecipitating p120. Binding partners are then selectively eluted and identified by single-dimension liquid-chromatography tandem mass spectrometry. Crosslinking dramatically improved the efficiency of p120 co-immunoprecipitation with other members of the
cadherin complex and revealed several new putative binding partners. Interestingly, one of these was the RhoA substrate p160 Rho Kinase (ROCK1). Using immunofluorescence and immunoprecipitation-based analyses, we showed that a fraction of ROCK1 associates with E-
cadherin-bound p120 at cell-cell junctions. ROCK1 depletion by shRNAt led to disorganization of the adherens junction, but did not effect p120 or E-
cadherin expression levels. Instead, disruption of the
cadherin complex appeared to be due to a disruption in junctional actin. Using an in vitro kinase assay and phospho-specific p120 antibodies, we demonstrated that ROCK1 phosphorylates p120 on serine 268. These data reveal that ROCK1 can phosphorylate and interact with p120, and implies a role for this interaction in regulating
cadherin stability.
Advisors/Committee Members: Alissa M. Weaver (Committee Chair).
Subjects/Keywords: crosslink; Rho Kinase; cadherin; proteomics; p120-catenin
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Smith, A. L. (2011). ReCLIP (Reversible Cross-Link Immuno-Precipitation) reveals a novel interaction between p120-catenin and p160 Rho Kinase. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/11028
Chicago Manual of Style (16th Edition):
Smith, Andrew Leslie. “ReCLIP (Reversible Cross-Link Immuno-Precipitation) reveals a novel interaction between p120-catenin and p160 Rho Kinase.” 2011. Doctoral Dissertation, Vanderbilt University. Accessed April 16, 2021.
http://hdl.handle.net/1803/11028.
MLA Handbook (7th Edition):
Smith, Andrew Leslie. “ReCLIP (Reversible Cross-Link Immuno-Precipitation) reveals a novel interaction between p120-catenin and p160 Rho Kinase.” 2011. Web. 16 Apr 2021.
Vancouver:
Smith AL. ReCLIP (Reversible Cross-Link Immuno-Precipitation) reveals a novel interaction between p120-catenin and p160 Rho Kinase. [Internet] [Doctoral dissertation]. Vanderbilt University; 2011. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/1803/11028.
Council of Science Editors:
Smith AL. ReCLIP (Reversible Cross-Link Immuno-Precipitation) reveals a novel interaction between p120-catenin and p160 Rho Kinase. [Doctoral Dissertation]. Vanderbilt University; 2011. Available from: http://hdl.handle.net/1803/11028
Vanderbilt University
18.
Stoops, Sydney Lear.
Discovery, Optimization, and Understanding the Mechanism of Action of Small Molecules that Restore E-cadherin Expression.
Degree: PhD, Pharmacology, 2012, Vanderbilt University
URL: http://hdl.handle.net/1803/11403
► E-cadherin is a transmembrane protein that maintains intercellular contacts and cellular polarity in epithelial tissues. The down-regulation of E-cadherin is thought to aid in the…
(more)
▼ E-
cadherin is a transmembrane protein that maintains intercellular contacts and cellular polarity in epithelial tissues. The down-regulation of E-
cadherin is thought to aid in the induction of an epithelial-to-mesenchymal (EMT) transition resulting in an increased potential for invasion into surrounding tissues and entry into the bloodstream. Loss of E-
cadherin has been observed in a variety of human tumors resulting from somatic mutations, chromosomal deletions, proteolytic cleavage of E-
cadherin, and most commonly silencing of the CDH1 gene promoter.
A novel High-throughput screen was developed to identify small molecules that restored E-
cadherin expression in the SW620 cell line followed by medicinal chemistry employing iterative analog library synthesis to better identify the structure-activity relationship. Preliminary optimization of the screening hit has shown it is possible to synthesize small molecules that have an improved ability to restore E-
cadherin expression compared to the initial screening hits.
Recent endeavors have been taken to elucidate the mechanism of action of these small molecules to restore E-
cadherin expression. Quantitative PCR analysis has shown that E-
cadherin mRNA expression occurs after 3 hours of treatment with active analogs, suggesting the small molecules are altering transcription of the CDH1 gene. This was supported by experiments conducted using various plasmid constructs containing truncated segments of the E-
cadherin promoter region and luciferase reporter. It was shown that active analogs had a significant increase in luciferase activity as compared to DMSO or an inactive analog, which were used as controls. More specifically, we were able to narrow the site of action the active analogs to a 200 bp fragment of the E-
cadherin promoter region.
Elucidation of the mechanism of action will aid in identifying the novel molecular target. Such information would allow for further development of more efficacious and potent small molecules as well as further research to understand the importance of this interaction in the role of EMT and as a therapeutic target.
Advisors/Committee Members: Professor Robert Coffey (committee member), Professor Stephen Fesik (committee member), Professor Lawrence Marnett (committee member), Professor Albert Reynolds (committee member), Professor Craig Lindsley (committee member), Professor Brian Wadzinski (Committee Chair).
Subjects/Keywords: EMT; E-Cadherin; Epithelial-Mesenchymal Transition
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Stoops, S. L. (2012). Discovery, Optimization, and Understanding the Mechanism of Action of Small Molecules that Restore E-cadherin Expression. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/11403
Chicago Manual of Style (16th Edition):
Stoops, Sydney Lear. “Discovery, Optimization, and Understanding the Mechanism of Action of Small Molecules that Restore E-cadherin Expression.” 2012. Doctoral Dissertation, Vanderbilt University. Accessed April 16, 2021.
http://hdl.handle.net/1803/11403.
MLA Handbook (7th Edition):
Stoops, Sydney Lear. “Discovery, Optimization, and Understanding the Mechanism of Action of Small Molecules that Restore E-cadherin Expression.” 2012. Web. 16 Apr 2021.
Vancouver:
Stoops SL. Discovery, Optimization, and Understanding the Mechanism of Action of Small Molecules that Restore E-cadherin Expression. [Internet] [Doctoral dissertation]. Vanderbilt University; 2012. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/1803/11403.
Council of Science Editors:
Stoops SL. Discovery, Optimization, and Understanding the Mechanism of Action of Small Molecules that Restore E-cadherin Expression. [Doctoral Dissertation]. Vanderbilt University; 2012. Available from: http://hdl.handle.net/1803/11403
Universidade Nova
19.
Marques, Filipa Gil.
The involvement of CDH1 in cancer angiogenesis.
Degree: 2011, Universidade Nova
URL: http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/6645
► Dissertação para obtenção do Grau de Mestre em Biotecnologia
Cancer is one of the leading causes of death worldwide. Biological hallmarks such as induced and…
(more)
▼ Dissertação para obtenção do Grau de Mestre em
Biotecnologia
Cancer is one of the leading causes of death worldwide. Biological hallmarks such as induced and sustained angiogenesis are implicated in tumour progression, as well as invasion and metastasis which are the major causes of cancer-related mortality. E-Cadherin impairment on the cell membrane is intimately related with invasion and metastasis. Also, increased levels of vascular endothelial growth factor (VEGF), an angiogenic marker, and its receptor on the plasma membrane can be implicated in tumour progression.
This work was focused on how the inactivation of E-Cadherin, a molecule associated to an invasive phenotype can be related with angiogenesis, probably through VEGF-A expression.
Two different cell lines without expression of E-Cadherin and stably transduced to express wild-type (WT) E-Cadherin were used to carry out this study: AGS Par/WT (from stomach) and MDA-435 Mock/WT (from breast). Immunohistochemical staining was performed to determine the cellular localization and western blot analysis was performed to assess the expression levels of E-Cadherin. VEGFA mRNA levels were assessed by quantitative Real-time PCR. Additionally, we determined the levels phosphorylated (phospho) ERK1/2, as well as the expression levels of total ERK1/2. To study the angiogenic role of E-cadherin the chick embryo Chorioallantoic Membrane (CAM) assay was used. We characterise in vivo the different cell lines concerning both angiogenic and tumorigenic responses dependent on E-Cadherin.
Only cell lines stably expressing WT human E-Cadherin showed levels of expression of this protein at the cell membrane regardless of their tissue of origin. In vitro, AGS and MDA-435 cells expressing WT E-Cadherin revealed an increased expression of VEGFA in comparison to the control although not statically significant. In addition, both phospho-ERK1/2 and total ERK1/2 presented similar levels of expression regardless of the tissue of origin and E-Cadherin expression. Both angiogenic and tumorigenic responses in AGS WT was significantly increased in comparison to the control. The MDA-435 WT cells revealed increased tumorigenic response in comparison to the control. Overall, these results suggest that E-Cadherin expression is important for micro-tumour formation as well as for neovascularisation but this effect is dependent on the in vivo context.
Advisors/Committee Members: Seruca, Raquel.
Subjects/Keywords: Cancer; E-cadherin; (Tumour-) Angiogenesis; VEGF-A
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Marques, F. G. (2011). The involvement of CDH1 in cancer angiogenesis. (Thesis). Universidade Nova. Retrieved from http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/6645
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Marques, Filipa Gil. “The involvement of CDH1 in cancer angiogenesis.” 2011. Thesis, Universidade Nova. Accessed April 16, 2021.
http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/6645.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Marques, Filipa Gil. “The involvement of CDH1 in cancer angiogenesis.” 2011. Web. 16 Apr 2021.
Vancouver:
Marques FG. The involvement of CDH1 in cancer angiogenesis. [Internet] [Thesis]. Universidade Nova; 2011. [cited 2021 Apr 16].
Available from: http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/6645.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Marques FG. The involvement of CDH1 in cancer angiogenesis. [Thesis]. Universidade Nova; 2011. Available from: http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/6645
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
20.
Sandquist, Elizabeth.
N-Cadherin Expression And EMT Progression In Arsenic- And Cadmium-Transformed Urotsa.
Degree: PhD, Biomedical Sciences, 2015, University of North Dakota
URL: https://commons.und.edu/theses/1830
► Environmental agents are common causes of bladder cancer. Specifically, arsenic (As3+) and cadmium (Cd2+) are known carcinogens implicated in the development of bladder cancer.…
(more)
▼ Environmental agents are common causes of bladder cancer. Specifically, arsenic (As3+) and cadmium (Cd2+) are known carcinogens implicated in the development of bladder cancer. Previous studies from our laboratory have shown that As3+ and Cd2+ can cause malignant transformation of normal immortalized bladder urothelial cells, which can form tumors when injected subcutaneous or intraperitoneal into nude mice. Microarray analysis of repeated metal transformation in parallel revealed that N-
cadherin was the most upregulated gene in As3+ transformants, and a top induced gene in Cd2+-transformed cells. The switch from E-
cadherin to N-
cadherin is a well-known indicator of the epithelial-to-mesenchymal transition occurring in bladder cancer. Further, N-
cadherin upregulation is correlated with tumor stage, increased recurrence, and decreased survival in patients. While the factors mediating the decrease in E-
cadherin expression are well-established, little is known of the factors regulating the increase in N-
cadherin expression. The goal of the present study was to determine how As3+ and Cd2+ regulate N-
cadherin expression, whether this expression is maintained in heterotransplant models, and if N-
cadherin is promoting the epithelial-to-mesenchymal transition in As3+- and Cd2+-transformed UROtsa cells in vitro. This work has demonstrated that N-
cadherin is induced in As3+- and Cd2+-transformed UROtsa cell lines, and that the expression is maintained in intraperitoneal, but not subcutaneous, tumor xenografts. Further, tumor-initiating cells derived from transformed UROtsa cells did not express N-
cadherin. This suggests that tumor microenvironment and heterogeneity of cell populations are important factors for the use of animal models in cancer research. The As3+ and Cd2+ UROtsa cell lines represent the initial phases of EMT in bladder cancer, and may demonstrate a unique EMT pathway specific to heavy metal carcinogens. Transcriptional regulation of N-
cadherin, which is mostly unknown, may be elucidated by the investigation of the transcription factor Twist and epigenetic regulation, particularly histone acetylation.
Advisors/Committee Members: Scott H. Garrett.
Subjects/Keywords: arsenic; bladder cancer; cadmium; N-cadherin; UROtsa
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sandquist, E. (2015). N-Cadherin Expression And EMT Progression In Arsenic- And Cadmium-Transformed Urotsa. (Doctoral Dissertation). University of North Dakota. Retrieved from https://commons.und.edu/theses/1830
Chicago Manual of Style (16th Edition):
Sandquist, Elizabeth. “N-Cadherin Expression And EMT Progression In Arsenic- And Cadmium-Transformed Urotsa.” 2015. Doctoral Dissertation, University of North Dakota. Accessed April 16, 2021.
https://commons.und.edu/theses/1830.
MLA Handbook (7th Edition):
Sandquist, Elizabeth. “N-Cadherin Expression And EMT Progression In Arsenic- And Cadmium-Transformed Urotsa.” 2015. Web. 16 Apr 2021.
Vancouver:
Sandquist E. N-Cadherin Expression And EMT Progression In Arsenic- And Cadmium-Transformed Urotsa. [Internet] [Doctoral dissertation]. University of North Dakota; 2015. [cited 2021 Apr 16].
Available from: https://commons.und.edu/theses/1830.
Council of Science Editors:
Sandquist E. N-Cadherin Expression And EMT Progression In Arsenic- And Cadmium-Transformed Urotsa. [Doctoral Dissertation]. University of North Dakota; 2015. Available from: https://commons.und.edu/theses/1830
University of Illinois – Chicago
21.
Klomp, Jennifer.
Dissecting the Role of c-Src in the Regulation of Adherens Junctions using Engineered Kinases.
Degree: 2017, University of Illinois – Chicago
URL: http://hdl.handle.net/10027/22221
► Using an inducible kinase system, Rapamycin Regulated kinase (RapR-kinase), we directly activated the Src family tyrosine kinases c-Src (Src) and Lyn in human pulmonary arterial…
(more)
▼ Using an inducible kinase system, Rapamycin Regulated kinase (RapR-kinase), we directly activated the Src family tyrosine kinases c-Src (Src) and Lyn in human pulmonary arterial endothelial cells. We found that Src induced a transient endothelial cell barrier enhancement phase followed by a subsequent increase in permeability. Conversely, Lyn activation resulted in only disruption of the endothelial cell barrier. Similarly, we found that activation of Src but not Lyn was able to increase the rate of barrier recovery following disruption via thrombin. Further investigation revealed that Src-mediated enhancement of the endothelial cell barrier relied on accumulation of adherens junction protein VE
cadherin, as well as rearrangement, and broadening of adherens junctions. In addition, we determined that phosphorylation of VE
cadherin residue Y731 was required for Src-mediated endothelial cell barrier enhancement. The ability to temporally monitor the effect of direct activation of a specific kinase allowed for the identification of novel Src-mediated roles in endothelial cell barrier regulation, demonstrating the utility of using an inducible kinase system. A major limitation of the RapR-kinase system was that it only enabled activation of a kinase and not inactivation. However, due to the dynamic nature of phosphorylation, a system that allows for both specific and rapid activation and inhibition is needed for more accurate re-capitulation and dissection of signaling cascades mediated by specific kinases. Therefore, we further modified the system to allow for transient activation. By combining the RapR-kinase method with the mutation of the “gate keeper” residue in the catalytic domain and using the allele specific inhibitor 1-Naphthyl-PP1, we successfully generated a highly efficient and specific method to transiently activate kinases. Using our engineered reversible Src kinase as a model, we demonstrated that the duration of its kinase signaling can be tightly controlled in living cells. By employing this approach, we identified morphological changes induced by transient activation of Src and demonstrated the role of sequential Src-PI3K and Src-Rac1 signaling in the regulation of cell morphology. Furthermore, we expanded the technique to the Serine/Threonine kinase p38 to demonstrate its broad applicability. In summary, we described a new approach that enables transient activation of a kinase in living cells and identified new Src-dependent mechanisms for influencing changes in endothelial cell barrier function. The ability to manipulate kinase activity for a finite amount of time therefore provides a biologically relevant method of dissecting individual kinase functions and their effects on downstream signaling pathways.
Advisors/Committee Members: Karginov, Andrei V (advisor), Komarova, Yulia (committee member), O'Bryan, John P (committee member), Mehta, Dolly (committee member), Tyner, Angela (committee member), Karginov, Andrei V (chair).
Subjects/Keywords: Kinase; Src; VE cadherin; Lyn; Rac1; PI3K
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Klomp, J. (2017). Dissecting the Role of c-Src in the Regulation of Adherens Junctions using Engineered Kinases. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/22221
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Klomp, Jennifer. “Dissecting the Role of c-Src in the Regulation of Adherens Junctions using Engineered Kinases.” 2017. Thesis, University of Illinois – Chicago. Accessed April 16, 2021.
http://hdl.handle.net/10027/22221.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Klomp, Jennifer. “Dissecting the Role of c-Src in the Regulation of Adherens Junctions using Engineered Kinases.” 2017. Web. 16 Apr 2021.
Vancouver:
Klomp J. Dissecting the Role of c-Src in the Regulation of Adherens Junctions using Engineered Kinases. [Internet] [Thesis]. University of Illinois – Chicago; 2017. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/10027/22221.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Klomp J. Dissecting the Role of c-Src in the Regulation of Adherens Junctions using Engineered Kinases. [Thesis]. University of Illinois – Chicago; 2017. Available from: http://hdl.handle.net/10027/22221
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Illinois – Chicago
22.
Juettner, Vanessa V.
VE-PTP Inhibits GEF-H1 to Stabilize VE-cadherin Junctions in Endothelial Cells.
Degree: 2019, University of Illinois – Chicago
URL: http://hdl.handle.net/10027/23645
► Vascular Endothelial Protein Tyrosine Phosphatase (VE-PTP) is an endothelial-specific phosphatase that stabilizes Vascular Endothelial (VE)-cadherin junctions. Although studies have focused on the role of VE-PTP…
(more)
▼ Vascular Endothelial Protein Tyrosine Phosphatase (VE-PTP) is an endothelial-specific phosphatase that stabilizes Vascular Endothelial (VE)-
cadherin junctions. Although studies have focused on the role of VE-PTP in dephosphorylating VE-
cadherin in the activated endothelium, little is known of VE-PTP’s role in the quiescent endothelial monolayer. Here we used the photo-convertible fluorescent protein, VE-
cadherin-Dendra2, to monitor VE-
cadherin dynamics at AJs in confluent endothelial monolayers. We discovered that VE-PTP stabilizes VE-
cadherin junctions by reducing the rate of VE-
cadherin internalization independently of its phosphatase activity. VE-PTP serves as an adaptor protein which through binding and inhibiting the RhoGEF, GEF-H1 modulates RhoA activity and tension across VE-
cadherin junctions. Overexpression of VE-PTP cytosolic domain mutant interacting with GEF-H1 in VE-PTP-depleted endothelial cells reduced GEF-H1 activity and restored VE-
cadherin dynamics at AJs. Thus, VE-PTP stabilizes VE-
cadherin junctions and restricts endothelial permeability through inhibiting GEF-H1, and thereby limits RhoA signaling at AJs and reduces the VE-
cadherin internalization rate.
Advisors/Committee Members: Malik, Asrar B (advisor), Komarova, Yulia A (committee member), Mehta, Dolly (committee member), Karginov, Andrei (committee member), Kitajewski, Jan (committee member), Malik, Asrar B (chair).
Subjects/Keywords: VE-PTP
VE-cadherin
GEF-H1
RhoA
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Juettner, V. V. (2019). VE-PTP Inhibits GEF-H1 to Stabilize VE-cadherin Junctions in Endothelial Cells. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/23645
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Juettner, Vanessa V. “VE-PTP Inhibits GEF-H1 to Stabilize VE-cadherin Junctions in Endothelial Cells.” 2019. Thesis, University of Illinois – Chicago. Accessed April 16, 2021.
http://hdl.handle.net/10027/23645.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Juettner, Vanessa V. “VE-PTP Inhibits GEF-H1 to Stabilize VE-cadherin Junctions in Endothelial Cells.” 2019. Web. 16 Apr 2021.
Vancouver:
Juettner VV. VE-PTP Inhibits GEF-H1 to Stabilize VE-cadherin Junctions in Endothelial Cells. [Internet] [Thesis]. University of Illinois – Chicago; 2019. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/10027/23645.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Juettner VV. VE-PTP Inhibits GEF-H1 to Stabilize VE-cadherin Junctions in Endothelial Cells. [Thesis]. University of Illinois – Chicago; 2019. Available from: http://hdl.handle.net/10027/23645
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
23.
APRILE, PAOLA.
Unravelling the role of mechanical cues on the chondrogenic differentiation of stem cells.
Degree: School of Engineering. Discipline of Mechanical & Manuf. Eng, 2019, Trinity College Dublin
URL: http://hdl.handle.net/2262/91120
► The inability of adult articular cartilage to regenerate has motivated the development of tissue engineering strategies to repair cartilage defects before they progress to osteoarthritis.…
(more)
▼ The inability of adult articular cartilage to regenerate has motivated the development of tissue engineering strategies to repair cartilage defects before they progress to osteoarthritis. Common cell based strategies employing autologous chondrocytes to treat cartilage lesions, often fail to promote hyaline cartilage repair. Mesenchymal stem cells / stromal cells (MSC) represent a promising cell type for cartilage tissue engineering, due to their relative ease of isolation, ability to proliferate extensively in vitro and differentiate along multiple pathways1-3. MSC differentiation can be influenced by the mechanical properties of their environment4. The objective of this dissertation was to examine the influence of intrinsic and extrinsic mechanical cues on the initiation of chondrogenesis of MSC seeded on top (2-Dimension) or encapsulated within (3-Dimension) hydrogels of defined stiffness. The development of an Interpenetrating Network (IPN) hydrogel system able to support cell growth in 2D and 3D, enabled the independent control of substrate rigidity (2D and 3D) and cell morphology (3D). A softer environment (2D and 3D) was correlated to enhanced upregulation of key chondrogenic markers and cell condensation. Contrary to the expectations, allowing the cells to spread in a soft 3D context greatly improved this chondrogenic response. Finally, the effect of biomaterial's mechanical properties and external forces was combined to the application of a physiological magnitude of Hydrostatic Pressure (HP) to mimic the physiological environment of a loaded knee joint. In this case, the chondrogenic differentiation of HP-stimulated cells resulted enhanced to a greater extent, when the mechanical perturbation was applied after the initiation of their chondrogenic commitment. Mechanical forces and local morphogen gradients greatly influence cartilage development, hence biomimetic cartilage repair strategies aiming to recapitulate the complex interplay of biophysical and biochemical cues, would open new possibilities for cartilage tissue regeneration5,6. The results described in this work evidenced the fundamental role of biophysical cues in regulating MSC biology and the importance of this information to inspire new biomimetic strategies for stem cell based cartilage regeneration procedures. REFERENCES 1. Johnstone, B., Hering, T. M., Caplan, A. I., Goldberg, V. M. & Yoo, J. U. In VitroChondrogenesis of Bone Marrow-Derived Mesenchymal Progenitor Cells. Exp. Cell Res. 238, 265-272 (1998). 2. Caplan, A. I. Mesenchymal stem cells. J. Orthop. Res. 9, 641-650 (1991). 3. Badylak, S. F., Weiss, D. J., Caplan, A. & Macchiarini, P. Engineered whole organs and complex tissues. Lancet 379, 943-52 (2012). 4. Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix Elasticity Directs Stem Cell Lineage Specification. Cell 126, 677-689 (2006). 5. Ingber, D. E. et al. Tissue Engineering and Developmental Biology: Going Biomimetic. Tissue Eng. 12, 3265-3283 (2007). 6. Mammoto, T., Mammoto, A. & Ingber, D. E. Mechanobiology and…
Advisors/Committee Members: Kelly, Daniel.
Subjects/Keywords: Hydrostatic pressure; Mechanobiology; YAP; N-cadherin
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
APRILE, P. (2019). Unravelling the role of mechanical cues on the chondrogenic differentiation of stem cells. (Thesis). Trinity College Dublin. Retrieved from http://hdl.handle.net/2262/91120
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
APRILE, PAOLA. “Unravelling the role of mechanical cues on the chondrogenic differentiation of stem cells.” 2019. Thesis, Trinity College Dublin. Accessed April 16, 2021.
http://hdl.handle.net/2262/91120.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
APRILE, PAOLA. “Unravelling the role of mechanical cues on the chondrogenic differentiation of stem cells.” 2019. Web. 16 Apr 2021.
Vancouver:
APRILE P. Unravelling the role of mechanical cues on the chondrogenic differentiation of stem cells. [Internet] [Thesis]. Trinity College Dublin; 2019. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/2262/91120.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
APRILE P. Unravelling the role of mechanical cues on the chondrogenic differentiation of stem cells. [Thesis]. Trinity College Dublin; 2019. Available from: http://hdl.handle.net/2262/91120
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
24.
Dykes, Keshia S.
Biophysical Characterization Of A Proline Mutant Of Neural Cadherin.
Degree: M.S. in Chemistry, Chemistry and Biochemistry, 2016, University of Mississippi
URL: https://egrove.olemiss.edu/etd/921
► Cadherins are calcium dependent glycoproteins whose homophilic interactions mediate cell-cell adhesion in solid tissues. They are comprised of an extracellular region, a transmembrane region and…
(more)
▼ Cadherins are calcium dependent glycoproteins whose homophilic interactions mediate cell-cell adhesion in solid tissues. They are comprised of an extracellular region, a transmembrane region and a cytoplasmic region. The extracellular region plays a critical role in
cadherin-mediated cell adhesion, and has five tandemly repeated ectodomains (ec1-ec5), with three calcium binding sites situated in each interface between the domains. Dimerization of
cadherin occurs through formation of adhesive interactions between extracellular domains of cadherins from neighboring cells. Adhesive interaction occurs at the interfaces of ec1 domains of two molecules originating from different cell surfaces. Dimerization is critically dependent on the binding of calcium. Neural and epithelial
cadherin (ncad and ecad) are very similar in sequence comparison, but differ in kinetics of dimer assembly and dimer affinity in the presence or absence of calcium. The single most obvious difference in the strand swapped interface is a proline in ncad and a glutamate in ecad in position 16. Our hypothesis is that the slow kinetics of dimer disassembly of ncad is due to the steric restrictions of proline in position 16 of ncad. The purpose of this research is to mutate the proline, in position 16 to alanine (p16a), in ncad to decrease the steric hindrance and study the effects of the mutation. Stability studies assess the effect the mutation has on the folding properties of the protein. Calcium binding experiments demonstrate whether the mutation affects the binding affinity of calcium. From the results, p16a lowers the stability of the protein, ca2+ binding affinity, and dimerization kinetics of ncad.
Advisors/Committee Members: Susan D. Pedigo, Davita Watkins, Walter E. Cleland.
Subjects/Keywords: Mutation; Ncad; Neural Cadherin; P16A; Chemistry
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Dykes, K. S. (2016). Biophysical Characterization Of A Proline Mutant Of Neural Cadherin. (Thesis). University of Mississippi. Retrieved from https://egrove.olemiss.edu/etd/921
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Dykes, Keshia S. “Biophysical Characterization Of A Proline Mutant Of Neural Cadherin.” 2016. Thesis, University of Mississippi. Accessed April 16, 2021.
https://egrove.olemiss.edu/etd/921.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Dykes, Keshia S. “Biophysical Characterization Of A Proline Mutant Of Neural Cadherin.” 2016. Web. 16 Apr 2021.
Vancouver:
Dykes KS. Biophysical Characterization Of A Proline Mutant Of Neural Cadherin. [Internet] [Thesis]. University of Mississippi; 2016. [cited 2021 Apr 16].
Available from: https://egrove.olemiss.edu/etd/921.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Dykes KS. Biophysical Characterization Of A Proline Mutant Of Neural Cadherin. [Thesis]. University of Mississippi; 2016. Available from: https://egrove.olemiss.edu/etd/921
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Toronto
25.
Fiorino, Cara Erica.
Examining Novel Factors that Influence Contact-dependent Osteoblast and Osteoclast Differentiation.
Degree: PhD, 2016, University of Toronto
URL: http://hdl.handle.net/1807/76405
► A dynamic equilibrium between bone destruction by osteoclasts and bone formation by osteoblasts is responsible for the maintenance of bone integrity, mineral homeostasis and protection…
(more)
▼ A dynamic equilibrium between bone destruction by osteoclasts and bone formation by osteoblasts is responsible for the maintenance of bone integrity, mineral homeostasis and protection from bone-related disease. As such, the focus of this work was to examine novel factors contributing to the contact-dependent differentiation of osteoblasts and osteoclasts. Osteoblast differentiation and maturation is stimulated by multiple external factors, two of which are ascorbic acid (AA) and bone morphogenetic protein-2 (BMP-2). Utilizing MC3T3-E1 cells and primary murine osteoblasts, we identified a novel role for EB1, a microtubule plus-end binding protein, during osteoblast differentiation. AA-stimulation strongly induced EB1 expression and EB1 knockdown significantly impaired the osteoblast differentiation program in both AA- and BMP-2-induced osteoblasts. Furthermore, we identified that EB1 function was important for the global stability of -catenin, a major signaling molecule in osteoblasts. Lastly, the influence of E-
cadherin, a cell-cell adhesion and recognition molecule, was investigated in AA-stimulated osteoblasts. Up-regulation of Cdh1 (E-
cadherin) paralleled that of Catnb (beta-catenin), and E-
cadherin blocking antibody treatment dampened osteoblast-specific gene expression.
E-
cadherin is also expressed in monocyte/macrophage cells, which are precursors to osteoclasts. Receptor activator of nuclear factor-ÎşB ligand (RANKL)-stimulated osteoclast differentiation involves a period of precursor expansion followed by multiple fusion events to generate a multinucleated osteoclast. Interestingly, our results indicated that E-
cadherin participated in early precursor interaction/recognition rather than during periods of osteoclast fusion. In both RAW 264.7 cells and primary murine macrophages, E-
cadherin expression and surface localization was highest during early osteoclast differentiation. Utilizing E-
cadherin blocking antibodies prior to the onset of fusion delayed osteoclast-specific gene expression and significantly impaired multinucleated osteoclast formation. Long-term imaging revealed that blocking E-
cadherin function prolonged the proliferative phase of the precursor population while concomitantly decreasing the proportion of migrating precursors; the lamellipodium and polarized membrane extensions were identified as principal sites of fusion, establishing migration as a requirement for osteoclast differentiation.
This work characterizes EB1 and E-
cadherin function during osteoblast differentiation and the E-
cadherin-mediated transition from proliferative to migratory activities during osteoclast differentiation. Taken together, both studies highlight the value of exploring the early intra- and intercellular events that direct osteoblast and osteoclast differentiation.
Advisors/Committee Members: Harrison, Rene E., Cell and Systems Biology.
Subjects/Keywords: differentiation; EB1; E-cadherin; osteoblast; osteoclast; 0379
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Fiorino, C. E. (2016). Examining Novel Factors that Influence Contact-dependent Osteoblast and Osteoclast Differentiation. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/76405
Chicago Manual of Style (16th Edition):
Fiorino, Cara Erica. “Examining Novel Factors that Influence Contact-dependent Osteoblast and Osteoclast Differentiation.” 2016. Doctoral Dissertation, University of Toronto. Accessed April 16, 2021.
http://hdl.handle.net/1807/76405.
MLA Handbook (7th Edition):
Fiorino, Cara Erica. “Examining Novel Factors that Influence Contact-dependent Osteoblast and Osteoclast Differentiation.” 2016. Web. 16 Apr 2021.
Vancouver:
Fiorino CE. Examining Novel Factors that Influence Contact-dependent Osteoblast and Osteoclast Differentiation. [Internet] [Doctoral dissertation]. University of Toronto; 2016. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/1807/76405.
Council of Science Editors:
Fiorino CE. Examining Novel Factors that Influence Contact-dependent Osteoblast and Osteoclast Differentiation. [Doctoral Dissertation]. University of Toronto; 2016. Available from: http://hdl.handle.net/1807/76405
University of Illinois – Urbana-Champaign
26.
Barry, Adrienne.
Mechanical regulation of cell-cell junctions.
Degree: PhD, 0318, 2015, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/73077
► Cadherins are cell-cell adhesion proteins that mediate cell recognition, segregation, and signaling in many tissues. Recent findings demonstrated that type I classical cadherin complexes are…
(more)
▼ Cadherins are cell-cell adhesion proteins that mediate cell recognition, segregation, and signaling in many tissues. Recent findings demonstrated that type I classical
cadherin complexes are mechanosensitive. Mechanical forces in the tissue environment play a profound role in the growth, morphogenesis, and physiology of
cadherin-expressing cells. In order to establish how force impinges on critical cell functions in healthy or diseased tissue, it is essential to determine the mechanisms by which mechanical force is transduced into biochemical signals. In this dissertation, I provide new mechanistic insights into how mechanics alters the organization and function of
cadherin-dependent adhesions, which are essential intercellular adhesions in all tissues. First, studies examined the dependence of GTPase signaling, associated with mechanotransduction, on
cadherin ligation. Dynamic fluorescence imaging examined Rac1 activation at nascent cell-cell junctions, and revealed qualitative correlations between measured
cadherin binding affinities and the signal amplitude triggered by
cadherin ligation. Second, I examined the role of the cytosolic protein α-catenin in E-
cadherin-based adhesion and mechanotransduction, using bead-twisting measurements in conjunction with confocal fluorescence imaging. These experiments revealed rapid, early molecular events in mechanotransduction and the rudiments of a mechanotransduction mechanism. I further investigated how internal contractile forces, regulated by the stiffness of the cell substrate, influence intercellular junction formation and signaling in endothelial monolayers. Finally, experiments focused on a more physiologically relevant problem: VE-
cadherin-mediated mechanotransduction in human pulmonary endothelial cells. These studies established that VE-
cadherin complexes are mechanosensitive, and provides direct evidence that the associated mechanotransduction regulates both local cytoskeletal remodeling and global cell mechanics. Moreover, studies revealed that
cadherin adhesions across the cell monolayer form a mechanosensitive network that regulates endothelial integrity in response to mechanical stimuli. These results suggest that VE-
cadherin mechanotransduction can significantly impact cell function not only at the single cell level, but also across the cell monolayer. These studies were followed by work examining a clinically relevant problem: how a disease-associated single nucleotide polymorphism (SNP) in cortactin, a cytoskeletal adaptor protein, affects the regulation of endothelial cell-cell junctions. Combined MTC and imaging experiments revealed insights into both the role of the cortactin SNP in VE-
cadherin mechanotransduction, and the functional implications of VE-
cadherin mechanotransduction. These findings have critical implications for endothelial homeostasis and disease.
Advisors/Committee Members: Leckband, Deborah E. (advisor), Leckband, Deborah E. (Committee Chair), Gennis, Robert B. (committee member), Brieher, William M. (committee member), Fratti, Rutilio A. (committee member).
Subjects/Keywords: Cadherin; Adhesion; mechanotransduction; magnetic twisting cytometry
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Barry, A. (2015). Mechanical regulation of cell-cell junctions. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/73077
Chicago Manual of Style (16th Edition):
Barry, Adrienne. “Mechanical regulation of cell-cell junctions.” 2015. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 16, 2021.
http://hdl.handle.net/2142/73077.
MLA Handbook (7th Edition):
Barry, Adrienne. “Mechanical regulation of cell-cell junctions.” 2015. Web. 16 Apr 2021.
Vancouver:
Barry A. Mechanical regulation of cell-cell junctions. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2015. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/2142/73077.
Council of Science Editors:
Barry A. Mechanical regulation of cell-cell junctions. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2015. Available from: http://hdl.handle.net/2142/73077
University of Edinburgh
27.
Teo, Katy Ann.
Elucidating biological mechanisms associated with invasive lobular carcinoma of the breast.
Degree: PhD, 2017, University of Edinburgh
URL: http://hdl.handle.net/1842/23628
► Breast cancer is a heterogeneous disease, and can be classified according to histological subtypes based on cellular morphology. Invasive ductal carcinoma (IDC) and invasive lobular…
(more)
▼ Breast cancer is a heterogeneous disease, and can be classified according to histological subtypes based on cellular morphology. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the most common histological subtypes, accounting for approximately 80% and 12% of cases respectively. ILC exhibits a number of distinct clinico-pathological features in comparison with IDC, and is understudied as a breast cancer subtype. ILC tumours are typically oestrogen receptor positive, HER2 negative, and frequently demonstrate early loss of Ecadherin expression, which is a hallmark of the lobular phenotype. ILC is presently treated in a similar manner to IDC, with treatment generally directed against hormone receptors. Upon acquisition of hormone resistance, limited secondary options are available; patients are rarely candidates for agents targeting HER2, and are recognised to be poorly responsive to chemotherapeutics. We therefore need to advance our understanding of lobular tumour biology, in order to identify suitable biomarkers that will guide the development of targeted therapies for ILC patients. As protein expression levels determine cellular phenotype, a protein-based approach has the potential to provide biologically relevant insight into the mechanisms driving ILC. A range of protein analysis platforms, including reverse phase protein array, label-free mass spectrometry and immunohistochemistry, were therefore used to elucidate biological mechanisms active in the ILC subtype. Such experiments led to the identification of activated PI3K-Akt signalling in mouse and human ILC, suggesting that inhibition of this pathway may be an effective treatment strategy in lobular breast cancer. Preliminary evidence of differences in cytoskeletal and extracellular matrix (ECM) proteins was also acquired, providing an interesting basis for future research. A further major strand of this project was the development of in vitro and in vivo tools, to facilitate further interrogation of lobular biology. This included determination of a representative mouse model of ILC, and generation of primary cancer cells and cancer-associated fibroblasts (CAFs) from patient-derived material. Analysis of CAFS showed differential expression of ECM-associated genes, consistent with proteomic analyses. In addition, a tissue micro-array (TMA) comprising primary ILC and IDC tumours, with associated clinical data, was developed. Immunohistochemical staining of the TMA identified a potential role for IGF-1 pathway signalling in ILC, with increased expression of IGF-1 ligand associating with increased tumour size and metastasis in ILC patients. Taken together, the generation and validation of a range of useful tools in the course of this work has provided useful insight into the unique biology of ILC.
Subjects/Keywords: 616.99; breast cancer; lobular; E-cadherin
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Teo, K. A. (2017). Elucidating biological mechanisms associated with invasive lobular carcinoma of the breast. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/23628
Chicago Manual of Style (16th Edition):
Teo, Katy Ann. “Elucidating biological mechanisms associated with invasive lobular carcinoma of the breast.” 2017. Doctoral Dissertation, University of Edinburgh. Accessed April 16, 2021.
http://hdl.handle.net/1842/23628.
MLA Handbook (7th Edition):
Teo, Katy Ann. “Elucidating biological mechanisms associated with invasive lobular carcinoma of the breast.” 2017. Web. 16 Apr 2021.
Vancouver:
Teo KA. Elucidating biological mechanisms associated with invasive lobular carcinoma of the breast. [Internet] [Doctoral dissertation]. University of Edinburgh; 2017. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/1842/23628.
Council of Science Editors:
Teo KA. Elucidating biological mechanisms associated with invasive lobular carcinoma of the breast. [Doctoral Dissertation]. University of Edinburgh; 2017. Available from: http://hdl.handle.net/1842/23628
Queens University
28.
Vanderlee, Amanda.
Reciprocal Regulation of E-Cadherin and SHP2 by the Extracellular CA2+-Sensing Receptor in Colonic Epithelial Adenocarcinoma Cells
.
Degree: Physiology, 2009, Queens University
URL: http://hdl.handle.net/1974/1943
► Colon cancer is characterized by the progressive loss of E-cadherin, a Ca2+-dependent adherens junction component and epithelial marker. Furthermore, inhibition of the phosphatase SHP2, essential…
(more)
▼ Colon cancer is characterized by the progressive loss of E-cadherin, a Ca2+-dependent adherens junction component and epithelial marker. Furthermore, inhibition of the phosphatase SHP2, essential in the cell survival signaling via the epidermal growth factor receptor pathway, has been shown to upregulate E-cadherin in breast cancer cell lines. This suggests that unregulated increases in SHP2 may promote a cancer cell phenotype. The aim of this study was to define molecular mechanisms by which dietary Ca2+ is chemoprotective against colon cancer. The extracellular Ca2+-sensing receptor (CaSR) has been implicated in this process and we speculated that there was a relationship between CaSR activation and E-cadherin and SHP2 expression levels on colonic epithelia. A colonic adenocarcinoma cell line which lacks endogenous E-cadherin expression, SW480, was used as a model cell. CaSR levels were manipulated by transient transfection and E-cadherin and SHP2 expression levels were determined by Western blotting. The E-cadherin expression pattern was also assessed with RT-PCR and immunocytochemistry. We found that after CaSR activation via Ca2+ or other known CaSR agonists (neomycin sulphate, spermine), E-cadherin expression was increased and SHP2 expression was decreased. However, the E-cadherin expression pattern was altered in the presence of a dominant-negative CaSR (R185Q). Furthermore, pharmacological inhibition of p38 MAPK inhibited CaSR-mediated increases of E-cadherin protein in SW480 cells. Inhibition of p38 MAPK had no effect on CaSR-stimulation of E-cadherin transcript or promoter activity. SHP2 decreases usually seen after Ca2+-treatment were reduced after pharmacological inhibition of JNK in the presence of high Ca2+. CaSR activation also increased cell-cell adherence as assessed by electronic cell sizing and this adherence was lost when both CaSR-mediated changes in E-cadherin and SHP2 expression were inhibited. We conclude that CaSR activation in colonic epithelial cancer cells stimulated E-cadherin increases, through a mechanism involving p38 MAPK, as well as inhibited SHP2 expression, through a JNK-mediated mechanism. Further, these protein changes post-CaSR activation cause an increase in cell-cell adherence. Our results suggest that the chemoprotective nature of dietary Ca2+ supplements may involve reciprocal regulation of E-cadherin and SHP2 via the CaSR.
Subjects/Keywords: E-Cadherin
;
CaSR
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Vanderlee, A. (2009). Reciprocal Regulation of E-Cadherin and SHP2 by the Extracellular CA2+-Sensing Receptor in Colonic Epithelial Adenocarcinoma Cells
. (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/1943
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Vanderlee, Amanda. “Reciprocal Regulation of E-Cadherin and SHP2 by the Extracellular CA2+-Sensing Receptor in Colonic Epithelial Adenocarcinoma Cells
.” 2009. Thesis, Queens University. Accessed April 16, 2021.
http://hdl.handle.net/1974/1943.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Vanderlee, Amanda. “Reciprocal Regulation of E-Cadherin and SHP2 by the Extracellular CA2+-Sensing Receptor in Colonic Epithelial Adenocarcinoma Cells
.” 2009. Web. 16 Apr 2021.
Vancouver:
Vanderlee A. Reciprocal Regulation of E-Cadherin and SHP2 by the Extracellular CA2+-Sensing Receptor in Colonic Epithelial Adenocarcinoma Cells
. [Internet] [Thesis]. Queens University; 2009. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/1974/1943.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Vanderlee A. Reciprocal Regulation of E-Cadherin and SHP2 by the Extracellular CA2+-Sensing Receptor in Colonic Epithelial Adenocarcinoma Cells
. [Thesis]. Queens University; 2009. Available from: http://hdl.handle.net/1974/1943
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Colorado State University
29.
Chernyavskaya, Yelena.
Voltage gated calcium channel β2 protein is required in the heart for control of cell proliferation and heart tube integrity, The.
Degree: PhD, Biology, 2011, Colorado State University
URL: http://hdl.handle.net/10217/70435
► L-type calcium channels regulate calcium (LTCC) entry into cardiomyocytes. CACNB2 (β2) LTCC auxiliary subunits traffic the pore-forming CACNA subunit to the membrane and modulate channel…
(more)
▼ L-type calcium channels regulate calcium (LTCC) entry into cardiomyocytes. CACNB2 (β2) LTCC auxiliary subunits traffic the pore-forming CACNA subunit to the membrane and modulate channel kinetics. β2 is a Membrane Associated Guanylate Kinase (MAGUK) protein. A major role of MAGUK proteins is to scaffold cellular junctions and multi-protein complexes. To investigate developmental functions for β2.1, we depleted it in zebrafish using morpholinos. β2.1-depleted embryos developed cardiac edema and lethal cardiac defects. Ventricular cardiomyocytes proliferated at a slower rate, and failed to elongate their cell shape, which led to dysmorphic cardiac morphology and weakened contractility. Reduction in proliferation was marked by smaller heart fields and an increase in bmp4, an anti-proliferative marker. Thus, β2.1 helps regulate heart size by regulating the rate of mitosis and bmp4 expression in the ventricle. Additionally, cardiomyocytes depleted for β2.1 failed to accumulate N-
cadherin at the membrane, and dissociated easily from neighboring myocytes under stress. Hence, we propose that β2 could function as a MAGUK scaffolding unit to maintain N-
cadherin-based adherens junctions and heart tube integrity. To test this hypothesis we mutated the β2.1 residues necessary for interaction with the LTCC and observed its expression in cardiomyocytes using a GFP tag. Mutant β2.1 was still able to localize to the membrane supporting the possibility that it has a role in maintaining other protein complexes, such as adherens junctions.
Advisors/Committee Members: Garrity, Deborah Marie (advisor), Mykles, Donald (committee member), Miller, Charles (committee member), Reddy, A.S.N. (committee member).
Subjects/Keywords: cardiac; development; LTCC; N-cadherin; adhesion; zebrafish
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chernyavskaya, Y. (2011). Voltage gated calcium channel β2 protein is required in the heart for control of cell proliferation and heart tube integrity, The. (Doctoral Dissertation). Colorado State University. Retrieved from http://hdl.handle.net/10217/70435
Chicago Manual of Style (16th Edition):
Chernyavskaya, Yelena. “Voltage gated calcium channel β2 protein is required in the heart for control of cell proliferation and heart tube integrity, The.” 2011. Doctoral Dissertation, Colorado State University. Accessed April 16, 2021.
http://hdl.handle.net/10217/70435.
MLA Handbook (7th Edition):
Chernyavskaya, Yelena. “Voltage gated calcium channel β2 protein is required in the heart for control of cell proliferation and heart tube integrity, The.” 2011. Web. 16 Apr 2021.
Vancouver:
Chernyavskaya Y. Voltage gated calcium channel β2 protein is required in the heart for control of cell proliferation and heart tube integrity, The. [Internet] [Doctoral dissertation]. Colorado State University; 2011. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/10217/70435.
Council of Science Editors:
Chernyavskaya Y. Voltage gated calcium channel β2 protein is required in the heart for control of cell proliferation and heart tube integrity, The. [Doctoral Dissertation]. Colorado State University; 2011. Available from: http://hdl.handle.net/10217/70435
California State University – Northridge
30.
Manohar, Subrajaa.
CDH11 is required for neural crest cell specification and survival.
Degree: MS, Biology, 2020, California State University – Northridge
URL: http://hdl.handle.net/10211.3/217398
► Neural crest (NC) cells are a multipotent embryonic population of stem-like cells that form various tissues in vertebrates including pigment cells, craniofacial bone and cartilage,…
(more)
▼ Neural crest (NC) cells are a multipotent embryonic population of stem-like cells that form various tissues in vertebrates including pigment cells, craniofacial bone and cartilage, and the peripheral nervous system. NC cells are ectoderm-derived progenitor cells that begin as neuroepithelial cells in the neural tube but detach and migrate throughout the body after undergoing an epithelial to mesenchymal transition (EMT). These cells express a variety of cell-cell adhesion molecules, including
cadherin proteins, which control their specification, EMT, and migration. Abnormal development of NC cells can lead to multiple congenital defects as well as NC-derived cancers such as neuroblastoma and melanoma. Here, we identify the role of
Cadherin-11 (CDH11) in early chicken NC development. CDH11 is a type II
cadherin protein that is crucial for NC cell migration in amphibian embryos, and also regulates cell survival, proliferation, and migration in cancer cells. Using immunohistochemistry, we determined that CDH11 protein has dynamic expression, which co-localizes with Sox2 in neural progenitor cells in early embryos. Then, as NC cells are specified in the dorsal neural tube and begin to undergo EMT, CDH11 becomes restricted to pre-migratory and migratory NC cells and is down regulated in the neural tube. Electroporation of a translation-blocking CDH11 morpholino at gastrula stages leads to a reduction of PAX7, SOX9, SNAI2 and SOX10-positive NC cells in the dorsal neural tube, but has no effect on more ventral neural tube cells marked by Sox2, suggesting that CDH11 is required specifically in NC cells. We determined that CDH11 is required for NC cell survival, as loss of CDH11 increases p53-mediated programmed-cell death, and blocking the p53 partially rescues the NC phenotype. Further, we have identified that CDH11 is expressed in multiple breast cancer cell lines, but that its intracellular localization differs. CDH11 is localized to the cytoplasm and nuclei of the cancer cells, changing with invasiveness, suggesting it has non-adhesion functions in those cells. Our findings demonstrate a requirement for CDH11 in early NC development, and may increase our understanding of early NC-related developmental defects.
Advisors/Committee Members: Rogers, Crystal (advisor), Medh, Rheem (committee member).
Subjects/Keywords: Cadherin-11; Dissertations, Academic – CSUN – Biology.
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Manohar, S. (2020). CDH11 is required for neural crest cell specification and survival. (Masters Thesis). California State University – Northridge. Retrieved from http://hdl.handle.net/10211.3/217398
Chicago Manual of Style (16th Edition):
Manohar, Subrajaa. “CDH11 is required for neural crest cell specification and survival.” 2020. Masters Thesis, California State University – Northridge. Accessed April 16, 2021.
http://hdl.handle.net/10211.3/217398.
MLA Handbook (7th Edition):
Manohar, Subrajaa. “CDH11 is required for neural crest cell specification and survival.” 2020. Web. 16 Apr 2021.
Vancouver:
Manohar S. CDH11 is required for neural crest cell specification and survival. [Internet] [Masters thesis]. California State University – Northridge; 2020. [cited 2021 Apr 16].
Available from: http://hdl.handle.net/10211.3/217398.
Council of Science Editors:
Manohar S. CDH11 is required for neural crest cell specification and survival. [Masters Thesis]. California State University – Northridge; 2020. Available from: http://hdl.handle.net/10211.3/217398
◁ [1] [2] [3] [4] [5] … [13] ▶
. 
Open Access Theses and Dissertations