subject:(Ezrin)

University of Debrecen

1. Takács, Zsolt. Ezrin fehérje bakteriális overexpressziójának optimalizálása .

Degree: DE – Természettudományi és Technológiai Kar – Biológiai és Ökológiai Intézet, 2014, University of Debrecen

URL: http://hdl.handle.net/2437/192318

► Összefoglalás Ismereteink alapján a TIMAP fehérje az endotél barriert szabályozza az ERM fehérjéken keresztül. Escherichia coli baktériumokba transzformáltuk a munkacsoportunk által készített pGEX4T2-ezrin plazmidot és… (more)

Subjects/Keywords: Ezrin fehérje; overexpresszió

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APA (6^th Edition):

Takács, Z. (2014). Ezrin fehérje bakteriális overexpressziójának optimalizálása . (Thesis). University of Debrecen. Retrieved from http://hdl.handle.net/2437/192318

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Takács, Zsolt. “Ezrin fehérje bakteriális overexpressziójának optimalizálása .” 2014. Thesis, University of Debrecen. Accessed January 16, 2021. http://hdl.handle.net/2437/192318.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Takács, Zsolt. “Ezrin fehérje bakteriális overexpressziójának optimalizálása .” 2014. Web. 16 Jan 2021.

Vancouver:

Takács Z. Ezrin fehérje bakteriális overexpressziójának optimalizálása . [Internet] [Thesis]. University of Debrecen; 2014. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/2437/192318.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Takács Z. Ezrin fehérje bakteriális overexpressziójának optimalizálása . [Thesis]. University of Debrecen; 2014. Available from: http://hdl.handle.net/2437/192318

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Queens University

2. Hoskin, Victoria. A Novel Regulatory Role of Ezrin in Promoting Breast Cancer Cell Invasion and Metastasis .

Degree: Pathology and Molecular Medicine, 2015, Queens University

URL: http://hdl.handle.net/1974/12945

► Metastasis is the leading cause of death for breast cancer patients and poses significant clinical challenges in the successful treatment of breast cancer. The cytoskeleton… (more)

Subjects/Keywords: Calpain ; Ezrin ; Metastasis ; Invasion

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APA (6^th Edition):

Hoskin, V. (2015). A Novel Regulatory Role of Ezrin in Promoting Breast Cancer Cell Invasion and Metastasis . (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/12945

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hoskin, Victoria. “A Novel Regulatory Role of Ezrin in Promoting Breast Cancer Cell Invasion and Metastasis .” 2015. Thesis, Queens University. Accessed January 16, 2021. http://hdl.handle.net/1974/12945.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hoskin, Victoria. “A Novel Regulatory Role of Ezrin in Promoting Breast Cancer Cell Invasion and Metastasis .” 2015. Web. 16 Jan 2021.

Vancouver:

Hoskin V. A Novel Regulatory Role of Ezrin in Promoting Breast Cancer Cell Invasion and Metastasis . [Internet] [Thesis]. Queens University; 2015. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1974/12945.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hoskin V. A Novel Regulatory Role of Ezrin in Promoting Breast Cancer Cell Invasion and Metastasis . [Thesis]. Queens University; 2015. Available from: http://hdl.handle.net/1974/12945

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Johannes Gutenberg Universität Mainz

3. Janke, Matthias. Atomic force microscopy of biomimetic systems.

Degree: 2008, Johannes Gutenberg Universität Mainz

URL: http://ubm.opus.hbz-nrw.de/volltexte/2008/1628/

► This thesis was driven by the ambition to create suitable model systems that mimic complex processes in nature, like intramolecular transitions, such as unfolding and… (more)

▼ This thesis was driven by the ambition to create suitable model systems that mimic complex processes in nature, like intramolecular transitions, such as unfolding and refolding of proteins, or intermolecular interactions between different cell compo-nents. Novel biophysical approaches were adopted by employing atomic force mi-croscopy (AFM) as the main measurement technique due to its broad diversity. Thus, high-resolution imaging, adhesion measurements, and single-molecule force distance experiments were performed on the verge of the instrumental capabilities. As first objective, the interaction between plasma membrane and cytoskeleton, me-diated by the linker protein ezrin, was pursued. Therefore, the adsorption process and the lateral organization of ezrin on PIP2 containing solid-supported membranes were characterized and quantified as a fundament for the establishment of a biomimetic model system. As second component of the model system, actin filaments were coated on functionalized colloidal probes attached on cantilevers, serving as sensor elements. The zealous endeavor of creating this complex biomimetic system was rewarded by successful investigation of the activation process of ezrin. As a result, it can be stated that ezrin is activated by solely binding to PIP2 without any further stimulating agents. Additional cofactors may stabilize and prolong the active conformation but are not essentially required for triggering ezrin’s transformation into an active conformation. In the second project, single-molecule force distance experiments were performed on bis-loop tetra-urea calix[4]arene-catenanes with different loading rates (increase in force per second). These macromolecules were specifically designed to investigate the rupture and rejoining mechanism of hydrogen bonds under external load. The entangled loops of capsule-like molecules locked the unbound state of intramolecular hydrogen bonds mechanically, rendering a rebinding observable on the experimental time scale. In conjunction with Molecular Dynamics simulations, a three-well potential of the bond rupture process was established and all kinetically relevant parameters of the experiments were determined by means of Monte Carlo simulations and stochastic modeling. In summary, it can be stated that atomic force microscopy is an invaluable tool to scrutinize relevant processes in nature, such as investigating activation mechanisms in proteins, as shown by analysis of the interaction between F-actin and ezrin, as well as exploring fundamental properties of single hydrogen bonds that are of paramount interest for the complete understanding of complex supramolecular structures.

Subjects/Keywords: Rasterkraftmikroskopie, Ezrin, Kraftspektroskopie; AFM, Ezrin, Force Spectroscopy; Chemistry and allied sciences

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APA (6^th Edition):

Janke, M. (2008). Atomic force microscopy of biomimetic systems. (Doctoral Dissertation). Johannes Gutenberg Universität Mainz. Retrieved from http://ubm.opus.hbz-nrw.de/volltexte/2008/1628/

Chicago Manual of Style (16^th Edition):

Janke, Matthias. “Atomic force microscopy of biomimetic systems.” 2008. Doctoral Dissertation, Johannes Gutenberg Universität Mainz. Accessed January 16, 2021. http://ubm.opus.hbz-nrw.de/volltexte/2008/1628/.

MLA Handbook (7^th Edition):

Janke, Matthias. “Atomic force microscopy of biomimetic systems.” 2008. Web. 16 Jan 2021.

Vancouver:

Janke M. Atomic force microscopy of biomimetic systems. [Internet] [Doctoral dissertation]. Johannes Gutenberg Universität Mainz; 2008. [cited 2021 Jan 16]. Available from: http://ubm.opus.hbz-nrw.de/volltexte/2008/1628/.

Council of Science Editors:

Janke M. Atomic force microscopy of biomimetic systems. [Doctoral Dissertation]. Johannes Gutenberg Universität Mainz; 2008. Available from: http://ubm.opus.hbz-nrw.de/volltexte/2008/1628/

Universiteit Utrecht

4. Zhang, Z. Protein-protein interactions involved in Rap1-mediated signal transduction.

Degree: 2007, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/19793

► Signal transduction pathways play important roles in cell differentiation, proliferation, and survival. Specific protein-protein interactions mediate the assemblies of protein complexes in response to different… (more)

▼ Signal transduction pathways play important roles in cell differentiation, proliferation, and survival. Specific protein-protein interactions mediate the assemblies of protein complexes in response to different signals therefore regulate the proper transmission of cellular signals. Inappropriate protein-protein interactions within signalling pathways can lead to many diseases, including cancer. Proteomics-based approaches, which enable the quantitative investigation of protein-protein interactions involved in signalling networks, provide us with techniques to define the molecules controlling various signalling pathways. The small GTPase Rap1 belongs to the Ras family and shares high similarity with Ras protein. Rap1 cycles between an inactive GDP-bound state and an active GTP-bound state. This cycle is regulated by guanine nucleotide exchange factors (GEFs), such as Epac and GTPase activating proteins (GAPs), such as Rap1GAP. The most well-established processes where Rap1 is involved in include integrin-mediated adhesion and cadherin-mediated cell-cell adhesion. The GEFs are regulated by second messengers and are part of a protein-protein network, which regulates their temporal and spatial activities. The objective of the work described in this thesis was to investigate how Rap1 signaling pathway is regulated and to identify and characterize signaling proteins that direct the Rap1 pathway. In chapter 2, we studied the relation between AF6 and Rap1. We show that the overexpression of AF6 inhibits Rap1 induced adhesion. In addition, knocking-down the endogenous AF6 increases adhesion. These results show that in Jurkat T cells, AF6 functions to buffer GTP-Rap in resting cells and negatively regulates Rap1 function. In chapter 3 we analyze three Rap-like pseudogenes (mRap1A-retro1, mRap1A-retro2 and hRap1B-retro) in mouse and human genome. We show that all three retrogenes are expressed and encode functional proteins. These proteins appeared to stay more in a GTP-bound state compared to wild type Rap1. More interestingly, they exhibit clear differences in their ability to induce cell adhesion and spreading. To gain more insight in the protein interaction network, which controls the spatial and temporal organisation of Rap specific GEFs we performed yeast two-hybrid screens using Epac and PDZ-GEF as baits. This is described in chapter 4 addendum. A general summary of the results is given and candidate proteins were discussed. In chapter 4 and chapter 5 we characterized in detail the interaction between ERM (Ezrin-Radixin-Moesin) proteins and Epac1. We show that both Ezrin and Radixin interact with Epac1 in an activation-dependent manner. The Ezrin/Radixin binding region was identified in the N-terminus of Epac1. Furthermore, we demonstrate that this region is also required for the localization of Epac1 at microvilli in fully polarized cells. We show that Ezrin couples the activation of the ?-adrenergic receptor to Rap1 signalling via the recruitment of Epac1. In chapter 5 a novel Radixin mutant was characterized. This…

Subjects/Keywords: Geneeskunde; Rap; cancer; signal transduction; AF6; ezrin; adhesion

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APA (6^th Edition):

Zhang, Z. (2007). Protein-protein interactions involved in Rap1-mediated signal transduction. (Doctoral Dissertation). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/19793

Chicago Manual of Style (16^th Edition):

Zhang, Z. “Protein-protein interactions involved in Rap1-mediated signal transduction.” 2007. Doctoral Dissertation, Universiteit Utrecht. Accessed January 16, 2021. http://dspace.library.uu.nl:8080/handle/1874/19793.

MLA Handbook (7^th Edition):

Zhang, Z. “Protein-protein interactions involved in Rap1-mediated signal transduction.” 2007. Web. 16 Jan 2021.

Vancouver:

Zhang Z. Protein-protein interactions involved in Rap1-mediated signal transduction. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2007. [cited 2021 Jan 16]. Available from: http://dspace.library.uu.nl:8080/handle/1874/19793.

Council of Science Editors:

Zhang Z. Protein-protein interactions involved in Rap1-mediated signal transduction. [Doctoral Dissertation]. Universiteit Utrecht; 2007. Available from: http://dspace.library.uu.nl:8080/handle/1874/19793

University of New South Wales

5. Phang, Juanita. Crystallographic studies of CLIC proteins and ezrin.

Degree: Physics, 2012, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/52641 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11314/SOURCE01?view=true

► The CLIC (Chloride Intracellular Channel) proteins are a family of highly conserved proteins that exist as both soluble proteins and integral membrane forms. There are… (more)

▼ The CLIC (Chloride Intracellular Channel) proteins are a family of highly conserved proteins that exist as both soluble proteins and integral membrane forms. There are six human members in the CLIC family (CLIC1-CLIC6). The CLIC proteins have been associated with many biological functions, from cell cycle regulation to the maintenance of cell structural integrity. It has been shown that CLIC proteins are capable of inserting into membranes and forming functional ion channels in the absence of other proteins in vitro. It has also been demonstrated that CLIC1 undergoes reversible redox controlled structural changes. However, the exact biological function and mechanism of CLIC proteins are still unclear.Recent publications indicate that CLIC protein function may involve protein-protein interactions or S-nitrosylation. It has been shown that CLIC5-A interacts with the ERM protein ezrin, a protein that functions as a cross-linker between the plasma membrane and the actin cytoskeleton. In addition, it has been demonstrated that S-nitrosylation induces nuclear translocation of CLIC4.In this thesis, the crystal structures of the FERM domain of ezrin (FERM-Ezrin), full-length ezrin, four CLIC1 Cys24 mutants (C24A, C24D, C24S and FLAG-C24S) and S-nitrosylated CLIC1 are presented. The structures of full-length ezrin (residues 1-297, 516-586) are missing the intermediate domain due to limited proteolysis that occurred without the addition of protease during crystallisation. I have shown that CLIC1 forms a weak non-covalent complex with ezrin in vitro. The complex formation involves the CLIC1 active site cysteine (Cys24) in its reduced state. I have demonstrated that CLIC1 and CLIC4 are S- nitrosylated in vitro where Cys59 and Cys89 are identified as the two S-nitrosylation sites in CLIC1 using protein crystallography. Advisors/Committee Members: Curmi, Paul, Physics, Faculty of Science, UNSW, Wilk, Krystyna, Physics, Faculty of Science, UNSW, Duff, Anthony, Australian Nuclear Science and Technology Organisation.

Subjects/Keywords: Crystal structure; CLIC; Ezrin; Protein-protein interaction; S-nitrosylation

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APA (6^th Edition):

Phang, J. (2012). Crystallographic studies of CLIC proteins and ezrin. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/52641 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11314/SOURCE01?view=true

Chicago Manual of Style (16^th Edition):

Phang, Juanita. “Crystallographic studies of CLIC proteins and ezrin.” 2012. Doctoral Dissertation, University of New South Wales. Accessed January 16, 2021. http://handle.unsw.edu.au/1959.4/52641 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11314/SOURCE01?view=true.

MLA Handbook (7^th Edition):

Phang, Juanita. “Crystallographic studies of CLIC proteins and ezrin.” 2012. Web. 16 Jan 2021.

Vancouver:

Phang J. Crystallographic studies of CLIC proteins and ezrin. [Internet] [Doctoral dissertation]. University of New South Wales; 2012. [cited 2021 Jan 16]. Available from: http://handle.unsw.edu.au/1959.4/52641 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11314/SOURCE01?view=true.

Council of Science Editors:

Phang J. Crystallographic studies of CLIC proteins and ezrin. [Doctoral Dissertation]. University of New South Wales; 2012. Available from: http://handle.unsw.edu.au/1959.4/52641 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11314/SOURCE01?view=true

6. Χαλμούκη, Παναγιώτα. Μελέτη του ρόλου των TNS4/CTEN, ezrin και paxillin στο βασικοκυτταρικό καρκίνωμα του δέρματος.

Degree: 2013, University of Patras

URL: http://hdl.handle.net/10889/8622

► Το βασικοκυτταρικό καρκίνωμα του δέρματος αποτελεί τον συχνότερο τύπο καρκίνου του δέρματος. Από τους διάφορους ιστολογικούς υποτύπους του βασικοκυτταρικού καρκινώματος, ο διηθητικός ιστολογικός υπότυπος συνοδεύεται… (more)

▼ Το βασικοκυτταρικό καρκίνωμα του δέρματος αποτελεί τον συχνότερο τύπο καρκίνου του δέρματος. Από τους διάφορους ιστολογικούς υποτύπους του βασικοκυτταρικού καρκινώματος, ο διηθητικός ιστολογικός υπότυπος συνοδεύεται από αυξημένη διηθητική ικανότητα, υψηλότερο κίνδυνο τοπικής υποτροπής και πιο επιθετική βιολογική συμπεριφορά. Σε προηγούμενη μελέτη μας στο ίδιο υλικό βασικοκυτταρικού καρκινώματος, δείξαμε ότι η υπερέκφραση της Integrin-linked kinase (ILK), της ακτίνης των λείων μυικών κυττάρων (α-SMA), της πυρηνικής β-κατενίνης, του μεταγραφικού παράγοντα Snail, καθώς και η μείωση της έκφρασης της Ε-καντχερίνης που συντελούν δείκτες επιθηλιομεσεγχυματικής μετατροπής σχετίζονται με αυξημένη ικανότητα διήθησης και επιθετική βιολογική συμπεριφορά. Η επιθηλιομεσεγχυματική μετατροπή (Epithelial mesencymal transition-EMT) είναι μια βιολογική διαδικασία που επιτρέπει στα επιθηλιακά κύτταρα να αποκτήσουν έναν μεσεγχυματικό κυτταρικό φαινότυπο με ενισχυμένη μεταναστευτική ικανότητα, διεισδυτικότητα, υψηλή αντίσταση στην απόπτωση και ικανότητα παραγωγής συστατικών της εξωκυττάριας θεμέλιας ουσίας. Κύρια χαρακτηριστικά της ΕΜΤ είναι η απώλεια των ζωνών πρόσφυσης, καθώς και η ανοδιοργάνωση του κυτταροσκελετού. Ο κυτταροσκελετός της ακτίνης, που αποτελείται από νημάτια ακτίνης και πρωτεΐνες που αλληλεπιδρούν και ρυθμίζουν την δυναμική του κυτταροσκελετού συμμετέχει σε πολλές σημαντικές κυτταρικές λειτουργίες όπως η κυτταρική κίνηση, η κυτταρική διαίρεση κ.α. και εμπλέκεται σημαντικά στην καρκινογένεση. Ο ανεξέλεγκτος πολλαπλασιασμός των νεοπλασματικών κυττάρων, καθώς και η ικανότητα διήθησης και μετάστασης σχετίζονται με μεταβολές του κυτταροσκελετού της ακτίνης. Οι πρωτεΐνες CTEN (COOH-Terminal tensin-like protein) και η παξιλλίνη εντοπίζονται στις περιοχές πρόσδεσης των κυττάρων μέσω ιντεγκρινών στην εξωκυττάρια ουσία όπου αλληλεπιδρούν με τον κυτταροκελετό ακτίνης και συμμετέχουν στην ρύθμιση οδών μεταγωγής σημάτων που ελέγχουν λειτουργίες όπως η κυτταρική κίνηση, η επιθήλιο μεσεγχυματική μετάβαση, η διήθηση και μετάσταση. Η εζρίνη, μια κυτταροπλασματική πρωτεΐνη συνδέει μόρια της πλασματικής μεμβράνης με τον κυτταροσκελετό της ακτίνης και εμπλέκεται και αυτή σημαντικά σε διεργασίες κυτταρικής μετανάστευσης καθώς και στην διήθηση και μετάσταση των καρκινικών κυττάρων. Προηγούμενες μελέτες υποστηρίζουν την συμμετοχή των πρωτείνων CTEN, εζρίνης και παξιλλίνης στην καρκινογένεση στον άνθρωπο. Ωστόσο λίγα είναι γνωστά για το ρόλο τους στο βασικοκυτταρικό καρκίνωμα του δέρματος. Σκοπός της παρούσας εργασίας ήταν η μελέτη της έκφρασης και του ρόλου των πρωτεϊνών CTEN, εζρίνης και παξιλλίνης στο βασικοκυτταρικό καρκίνωμα του δέρματος. Για το σκοπό αυτό μελετήσαμε ανοσοϊστοχημικά την έκφραση αυτών των πρωτεϊνών που σχετίζονται με τον κυτταροσκελετό της ακτίνης σε 76 περιστατικά βασικοκυτταρικού καρκινώματος και εξετάσαμε την πιθανή συσχέτιση της έκφρασής τους με παραμέτρους που έχουν προγνωστική σημασία, όπως ο ιστολογικός υπότυπος, ο βαθμός κινδύνου και το επίπεδο διήθησης των όγκων. Ακόμη ελέγχθηκε η πιθανή συσχέτιση με την έκφραση… Advisors/Committee Members: Μπράβου, Βασιλική, Chalmouki, Panagiota, Μπράβου, Βασιλική, Παπαδάκη, Ελένη, Ασημακοπούλου, Μάρθα.

Subjects/Keywords: Βασικοκυτταρικό καρκίνωμα; Δέρμα; 616.994 77; Basal cell carcinoma; Ezrin; Paxillin; TNS4; CTEN

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Χαλμούκη, �. (2013). Μελέτη του ρόλου των TNS4/CTEN, ezrin και paxillin στο βασικοκυτταρικό καρκίνωμα του δέρματος. (Masters Thesis). University of Patras. Retrieved from http://hdl.handle.net/10889/8622

Chicago Manual of Style (16^th Edition):

Χαλμούκη, Παναγιώτα. “Μελέτη του ρόλου των TNS4/CTEN, ezrin και paxillin στο βασικοκυτταρικό καρκίνωμα του δέρματος.” 2013. Masters Thesis, University of Patras. Accessed January 16, 2021. http://hdl.handle.net/10889/8622.

MLA Handbook (7^th Edition):

Χαλμούκη, Παναγιώτα. “Μελέτη του ρόλου των TNS4/CTEN, ezrin και paxillin στο βασικοκυτταρικό καρκίνωμα του δέρματος.” 2013. Web. 16 Jan 2021.

Vancouver:

Χαλμούκη �. Μελέτη του ρόλου των TNS4/CTEN, ezrin και paxillin στο βασικοκυτταρικό καρκίνωμα του δέρματος. [Internet] [Masters thesis]. University of Patras; 2013. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10889/8622.

Council of Science Editors:

Χαλμούκη �. Μελέτη του ρόλου των TNS4/CTEN, ezrin και paxillin στο βασικοκυτταρικό καρκίνωμα του δέρματος. [Masters Thesis]. University of Patras; 2013. Available from: http://hdl.handle.net/10889/8622

Queens University

7. Mak, Hannah. The Ezrin Signalling Network as a Potential Novel Marker in Breast Cancer Metastasis .

Degree: Pathology and Molecular Medicine, 2010, Queens University

URL: http://hdl.handle.net/1974/5599

► Metastasis is the leading cause of mortality in human breast cancer. However, there are few predictive, prognostic, or therapeutic targets of breast cancer metastasis. Ezrin,… (more)

▼ Metastasis is the leading cause of mortality in human breast cancer. However, there are few predictive, prognostic, or therapeutic targets of breast cancer metastasis. Ezrin, a membrane cytoskeletal cross-linker, is frequently over-expressed in human breast cancer and is required for motility and invasion by cultured epithelial cells. Our group has recently shown that ezrin acts co-operatively with the non-receptor tyrosine kinase, Src, in the transformation of epithelial cells, in which ezrin is phosphorylated on specific tyrosines, such as Y477, by Src (91, 93). We therefore examined whether Src/ezrin interaction also regulates invasion and metastasis of breast cancer. This thesis presents the following results: 1) In a murine system, ezrin and Src are differentially localized in nulliparous, lactating mammary glands and PyMT-induced tumours, with pronounced apical expression in nulliparous mammary glands but non-polarized strong cytoplasmic expression in PyMT-induced tumours. 2) Increased expression and activation of ezrin, Src and Met in PyMT-induced tumours compared to normal breast tissues was observed. A concomitant increased expression of activated Stat3 and HGF was also observed in PyMT-induced tumours, consistent with the establishment of an HGF/Met autocrine loop. 3) In invasive human breast tumours, from a premenopausal patient cohort, ezrin showed significantly greater cytoplasmic localization compared to non-neoplastic epithelial ducts in normal mammoplasties. 4) In a mouse breast carcinoma xenograft model, a Y477F ezrin mutant (not phosphorylatable by Src), significantly reduced local invasion of primary tumours and spreading into visceral organs, yet, it did not significantly affect primary tumour growth rate. 5) Y477F ezrin-expressing tumours exhibited focal areas of incomplete membranous ezrin staining which was absent in control tumours. Moderate/strong cytoplasmic ezrin staining was evident in both tumour groups. Thus, ezrin is differentially localized in non-invasive versus invasive mammary tumours. Our study implicates a role of the Src/ezrin pathway in regulating local invasion and metastasis of breast carcinoma cells and provides a clinically relevant model for assessing the Src/ezrin pathway as a potential prognostic marker and treatment target for invasive breast cancer.

Subjects/Keywords: Src ; Ezrin ; Breast cancer ; Invasion ; Metastasis

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APA (6^th Edition):

Mak, H. (2010). The Ezrin Signalling Network as a Potential Novel Marker in Breast Cancer Metastasis . (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/5599

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mak, Hannah. “The Ezrin Signalling Network as a Potential Novel Marker in Breast Cancer Metastasis .” 2010. Thesis, Queens University. Accessed January 16, 2021. http://hdl.handle.net/1974/5599.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mak, Hannah. “The Ezrin Signalling Network as a Potential Novel Marker in Breast Cancer Metastasis .” 2010. Web. 16 Jan 2021.

Vancouver:

Mak H. The Ezrin Signalling Network as a Potential Novel Marker in Breast Cancer Metastasis . [Internet] [Thesis]. Queens University; 2010. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1974/5599.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mak H. The Ezrin Signalling Network as a Potential Novel Marker in Breast Cancer Metastasis . [Thesis]. Queens University; 2010. Available from: http://hdl.handle.net/1974/5599

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Queens University

8. Szeto, Alvin. Automated Quantification and Clinical Implications of Src, Ezrin, and Tks5 in Breast Cancer .

Degree: Pathology and Molecular Medicine, 2013, Queens University

URL: http://hdl.handle.net/1974/8107

► Breast cancer (BC) is one of the leading causes of cancer-related deaths in Canadian women. Aggressive BCs (e.g. triple-negative subtype; TN) present a clinical challenge… (more)

▼ Breast cancer (BC) is one of the leading causes of cancer-related deaths in Canadian women. Aggressive BCs (e.g. triple-negative subtype; TN) present a clinical challenge as defined biomarkers, particularly those indicative of unique cancer-associated signaling pathways, are needed to improve prognostication and prediction of therapeutic response. Overexpression of Src and its substrates, Ezrin and Tks5, have been associated with poor prognosis in many cancers. We have previously shown that Ezrin regulates proteolytic-independent invasion, while others have shown that Tks5 is associated with proteolytic-dependent invasion. Thus, expression of Ezrin versus Tks5 in BC cases may represent different invasion modalities. Additionally, immunofluorescence (IF)-based technologies may provide a more quantitative and objective approach for analysis of biomarker expression and subcellular compartmentalization compared to immunohistochemistry (IHC). In this study, I hypothesize that expression and subcellular localization of Src, Ezrin and Tks5, have improved prognostic significance in BCs, compared to current clinico-pathological parameters. To assess this, I optimized an IF-based automated quantification analysis (AQUA) system to measure subcellular expression in a 63-patient BC cohort and tested associations with clinico-pathological data. This thesis presents that: 1) Expression of Src and Ezrin increased, but that of Tks5 decreased in breast tumours compared to normal breast. 2) Src and Ezrin localized to the apical regions of normal breast epithelia but shifted to the cytoplasm in breast tumours. Tks5 exhibited a granular basal expression in normal breast epithelia, and is weakly expressed in tumour cellular compartments. 3) In our 63-patient cohort, Src and Ezrin had significant correlations with multiple clinico-pathological parameters, including TN status and lymphovascular invasion. 4) Clinico-pathological associations with IF-based AQUA scoring are directly comparable to conventional manual IHC scoring. Our study supports the role of Src and Ezrin as potential prognostic biomarkers for BC.

Subjects/Keywords: Ezrin ; Tks5 ; immunohistochemistry ; Automated Quantification ; TMA ; Tissue Microarray ; Src ; Immunofluorescence ; Breast cancer

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Szeto, A. (2013). Automated Quantification and Clinical Implications of Src, Ezrin, and Tks5 in Breast Cancer . (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/8107

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Szeto, Alvin. “Automated Quantification and Clinical Implications of Src, Ezrin, and Tks5 in Breast Cancer .” 2013. Thesis, Queens University. Accessed January 16, 2021. http://hdl.handle.net/1974/8107.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Szeto, Alvin. “Automated Quantification and Clinical Implications of Src, Ezrin, and Tks5 in Breast Cancer .” 2013. Web. 16 Jan 2021.

Vancouver:

Szeto A. Automated Quantification and Clinical Implications of Src, Ezrin, and Tks5 in Breast Cancer . [Internet] [Thesis]. Queens University; 2013. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1974/8107.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Szeto A. Automated Quantification and Clinical Implications of Src, Ezrin, and Tks5 in Breast Cancer . [Thesis]. Queens University; 2013. Available from: http://hdl.handle.net/1974/8107

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

9. Lindholm, Andreas. Ezrin som prognosmarkör för rektalcancer.

Degree: 2015, , Faculty of Health and Society (HS)

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-26644

►

Rektalcancer drabbar cirka 2000 personer i Sverige per år. Trots förbättringar i preoperativ utredning och behandling, utgör fortfarande lokalrecidiv (lokalt återfall i bäckenet) ett… (more)

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Rektalcancer drabbar cirka 2000 personer i Sverige per år. Trots förbättringar i preoperativ utredning och behandling, utgör fortfarande lokalrecidiv (lokalt återfall i bäckenet) ett allvarligt problem. I dagsläget överlever inte majoriteten av patienterna som får ett lokalrecidiv. För närvarande finns det inga kliniskt introducerade prognostiska vävnadsmarkörer för risken att utveckla ett lokalrecidiv. Identifieringen av en sådan markör skulle kunna leda till att en individuell behandlingsplan skapas för patienten, både primärt och postoperativt samt för uppföljning. Patienter med högre risk att utveckla lokalrecidiv skulle identifieras i ett tidigare skede. Proteinet ezrin har rapporterats vara en potentiell tumörmarkör vid olika cancerformer. Association mellan ett högt uttryck av ezrin och dålig prognos har påvisats. Syftet med studien var att undersöka om ezrin är en prognosmarkör för rektalcancer. Därigenom skulle eventuellt en förbättrad individbaserad behandlingsplan kunna skapas. Detta genom framställning av vävnadsklotsar med tekniken tissue microarray för att därefter utföra immunhistokemisk färgning för detektion av förekomsten av ezrin. Patienterna utgör en kontrollgrupp omfattande patienter som inte har utvecklat lokalrecidiv. I en case-only studie av Jörgren et al. (2010), med patienter som utvecklat lokalrecidiv fem år från primäroperation, visades att ezrin skulle kunna vara användbar som en prognosmarkör för rektalcancer. I 19,4 % (59/304) bedömdes färgintensiteten i vävnadscytoplasman som svag, som måttlig i 56,9 % (173/304) och som intensiv i 23,7 % (72/304). Intensiteten av cytoplasmafärgningen för ezrin ska analyseras multivariat och dess eventuella prognostiska betydelse värderas.

Yearly, about 2000 persons in Sweden are diagnosed with rectal cancer. Although advances have been made in tumour detection and its treatment, local recurrence still represents a severe matter. A majority of the patients diagnosed with local recurrence will not survive. There are no clinically available prognostic tissue markers for rectal cancer patients concerning the risk of local recurrence at the moment. The identification of a prognostic marker could lead to the development of an individualized treatment plan for the patient, both primarily and postoperatively as well as in follow-up. Several published papers have shown that the protein ezrin could be a potential tumour marker in various tumours. Association between high ezrin expression and poor prognosis has been demonstrated. The aim of this study was to further explore if ezrin may function as a prognostic marker for rectal. This by manufacturing tissue blocks utilizing the technique of tissue microarray that were stained immunohistochemically for ezrin. By analysing the expression of ezrin in the tumour cell cytoplasms microscopically by determining the colour intensity. Patients in the study form a control group consisting of only patients that did not develop a local recurrence. The ezrin expression of the control group will be compared to…

Subjects/Keywords: ezrin; immunhistokemi; lokalrecidiv; prognosmarkör; rektalcancer; tissue microarray; tumörmarkör; Medical and Health Sciences; Medicin och hälsovetenskap

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lindholm, A. (2015). Ezrin som prognosmarkör för rektalcancer. (Thesis). , Faculty of Health and Society (HS). Retrieved from http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-26644

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lindholm, Andreas. “Ezrin som prognosmarkör för rektalcancer.” 2015. Thesis, , Faculty of Health and Society (HS). Accessed January 16, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-26644.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lindholm, Andreas. “Ezrin som prognosmarkör för rektalcancer.” 2015. Web. 16 Jan 2021.

Vancouver:

Lindholm A. Ezrin som prognosmarkör för rektalcancer. [Internet] [Thesis]. , Faculty of Health and Society (HS); 2015. [cited 2021 Jan 16]. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-26644.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lindholm A. Ezrin som prognosmarkör för rektalcancer. [Thesis]. , Faculty of Health and Society (HS); 2015. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-26644

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universiteit Utrecht

10. Zhao, Jun. Subcellular localisation of Epac.

Degree: 2006, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/12552

► Cyclic adenosine 3', 5'- monophosphate (cAMP) is a second messenger that functions through binding to its downstream targets protein kinase A (PKA), cyclic-regulated ion channels… (more)

▼ Cyclic adenosine 3', 5'- monophosphate (cAMP) is a second messenger that functions through binding to its downstream targets protein kinase A (PKA), cyclic-regulated ion channels (CNG channels) and Epac1 (exchange protein directly activated by cAMP). Epac1 is guanine nucleotide exchange factor toward both Rap1 and Rap2. It is kept in the inactive conformation by an intramolecular interaction between the regulatory and catalytic domain. Binding of cAMP to the cAMP binding domain liberates the catalytic domain, resulting in the activation of Epac. In order to visualize the conformational change between inactivate- and active- state of Epac, a CFP-Epac-YFP probe was generated and fluorescence resonance energy transfer (FRET) between the two fluorescent moieties was monitored in vivo. The FRET signal was rapidly decreased in response to cAMP-raising agents, whereas it fully recovers after addition of cAMP-lowering agonists. This indicates that cAMP causes a significant conformational change in vivo and supports the unfolding model for Epac1 activation. To unravel more functions of Epac1, a series of Epac1 antibodies (Abs) were generated and characterized. 5D3, one of Epac1 monoclonal Abs, was further characterized based on its ability to recognize activate conformation Epac1. In vitro, the epitope of 5D3 was mapped within the cAMP binding domain, especially around Leucine 273. This region is hidden during autoinhibition. Using Epac1 Abs, subcellular localization of Epac1 was investigated in detail. Epac1 is mainly distributed around perinuclear region, especially in the endoplasmatic reticulum and the Golgi apparatus, as well as in the plasma membrane, especially at microvilli in fully polarized cells. Functional domains which are responsible for proper localization of Epac1 were also analyzed in detail. Our results revealed that both DEP domain and the EzB domain (the first 49 aa) are required for correct localization of Epac1 and the activation of Rap. The EzB domain is not only responsible but also sufficient for targeting Epac1 at microvilli. In contrast the DEP domain is only responsible for membrane localisation. Importantly, the microvillar localization is through binding to Ezrin/Radixin, proteins that function as linkers between the actin cytoskeleton and the apical membrane of polarized cells and as scaffold protein for protein complexes. The functional relevance of this interaction is still unclear, but the mere fact that Epac1 only binds to the active form of Ezrin/Radixin indicates that activation of these proteins is a crucial step in the spatial regulation of Epac1. Nuclear accumulation of Epac was also observed after removing the EzB domain. This effect could be mimicked by stimulation of the cells with HGF, that induces cell scattering, and with overexpression of RapV12 that induces cell spreading. These results suggest that upon loss of cell polarity and thus disruption of the apical structures, part of Epac1 translocation to the nucleus. However, the function of Epac1 in the nucleus remains a question…

Subjects/Keywords: Biologie; Epac; FRET probe; epitope mapping; Ezrin; microvilli

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❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhao, J. (2006). Subcellular localisation of Epac. (Doctoral Dissertation). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/12552

Chicago Manual of Style (16^th Edition):

Zhao, Jun. “Subcellular localisation of Epac.” 2006. Doctoral Dissertation, Universiteit Utrecht. Accessed January 16, 2021. http://dspace.library.uu.nl:8080/handle/1874/12552.

MLA Handbook (7^th Edition):

Zhao, Jun. “Subcellular localisation of Epac.” 2006. Web. 16 Jan 2021.

Vancouver:

Zhao J. Subcellular localisation of Epac. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2006. [cited 2021 Jan 16]. Available from: http://dspace.library.uu.nl:8080/handle/1874/12552.

Council of Science Editors:

Zhao J. Subcellular localisation of Epac. [Doctoral Dissertation]. Universiteit Utrecht; 2006. Available from: http://dspace.library.uu.nl:8080/handle/1874/12552

11. Assáo, Agnes. Correlação da expressão de podoplanina, ezrina e Rho-A em carcinomas espinocelulares de lábio inferior.

Degree: Mestrado, Patologia Bucal, 2015, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/25/25150/tde-02062015-113816/ ;

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A localização da podoplanina e da ezrina nas células malignas sugere uma ligação dessas proteínas nos processos de migração e invasão tumoral, ativadas mediante a… (more)

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A localização da podoplanina e da ezrina nas células malignas sugere uma ligação dessas proteínas nos processos de migração e invasão tumoral, ativadas mediante a fosforilação de Rho-A. O objetivo desse estudo foi avaliar a distribuição e a correlação da podoplanina, da ezrina e da Rho-A em 91 carcinomas espinocelulares de lábio inferior, e verificar a associação dessas proteínas com as variáveis clínicas e patológicas, com a evolução e com o prognóstico dos pacientes. Os pacientes foram analisados quanto ao gênero, idade, tabagismo, etilismo, classificação pelo sistema TNM, tratamento, ocorrência de recidivas locorregionais, segundo tumor primário, além da presença de embolização vascular, infiltração perineural, muscular, glandular e comprometimento linfonodal histopatológico. Analisou-se também as expressões imuno-histoquímicas de podoplanina, ezrina e Rho-A no front de invasão tumoral e o índice de malignidade tumoral. A associação entre a podoplanina, a ezrina e a Rho-A com as variáveis clínico-patológicas e a correlação entre as proteínas foram analisadas pelos testes do qui-quadrado e de Spearman, respectivamente. A análise da sobrevivência global em 5 e 10 anos foi feita pelo estimador produto-limite Kaplan-Meier e a comparação da curva de sobrevivência pelo teste log-rank. Os resultados demonstraram uma forte expressão de podoplanina, de ezrina e de Rho-A no front de invasão dos carcinomas espinocelulares de lábio inferior. Houve uma associação significativa entre a expressão citoplasmática de podoplanina com o etilismo (p=0,024), com a recidiva locorregional (p=0,028) e com comprometimento linfonodal histopatológico (p=0,010), porém não foi detectada nenhuma associação significativa entre a ezrina e a Rho-A com as variáveis clínicas e microscópicas analisadas. Uma correlação positiva e estatisticamente significativa entre a expressão de podoplanina membranosa (p=0,000 e r =0,384) e citoplasmática (p=0,000 e r=0,344) com a expressão de ezrina, e da podoplanina membranosa com a expressão de Rho-A (p=0,006 e r=0,282) foi detectada. Nenhuma das três proteínas se mostrou fator de prognóstico significativo para os pacientes com câncer de lábio. Concluímos que a forte expressão membranosa de podoplanina nos carcinomas espinocelulares de lábio inferior pode ajudar a identificar pacientes com menor risco de recidiva locorregional. Além disso, a correlação entre as expressões da podoplanina, da ezrina e da Rho-A pelas células neoplásicas sugere uma participação conjunta destas proteínas nos processos de movimentação celular e invasão tumoral do câncer de lábio.

Immunolocalization of podoplanin and ezrin suggests a connection between these proteins in migration and tumoral invasion process, activated through Rho-A phosphorylation. The aim of this study was to evaluate the distribution and the correlation of podoplanin, ezrin and Rho-A in 91 squamous cells carcinomas of the lower lip and to verify its association with clinical and pathological features, evolution and prognostic of the…

Advisors/Committee Members: Oliveira, Denise Tostes.

Subjects/Keywords: Câncer de lábio; Carcinoma espinocelular; Ezrin; Ezrina; Lip cancer; Podoplanin; Podoplanina; Rho-A; Rho-A; Squamous cell carcinoma

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Assáo, A. (2015). Correlação da expressão de podoplanina, ezrina e Rho-A em carcinomas espinocelulares de lábio inferior. (Masters Thesis). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/25/25150/tde-02062015-113816/ ;

Chicago Manual of Style (16^th Edition):

Assáo, Agnes. “Correlação da expressão de podoplanina, ezrina e Rho-A em carcinomas espinocelulares de lábio inferior.” 2015. Masters Thesis, University of São Paulo. Accessed January 16, 2021. http://www.teses.usp.br/teses/disponiveis/25/25150/tde-02062015-113816/ ;.

MLA Handbook (7^th Edition):

Assáo, Agnes. “Correlação da expressão de podoplanina, ezrina e Rho-A em carcinomas espinocelulares de lábio inferior.” 2015. Web. 16 Jan 2021.

Vancouver:

Assáo A. Correlação da expressão de podoplanina, ezrina e Rho-A em carcinomas espinocelulares de lábio inferior. [Internet] [Masters thesis]. University of São Paulo; 2015. [cited 2021 Jan 16]. Available from: http://www.teses.usp.br/teses/disponiveis/25/25150/tde-02062015-113816/ ;.

Council of Science Editors:

Assáo A. Correlação da expressão de podoplanina, ezrina e Rho-A em carcinomas espinocelulares de lábio inferior. [Masters Thesis]. University of São Paulo; 2015. Available from: http://www.teses.usp.br/teses/disponiveis/25/25150/tde-02062015-113816/ ;

12. Iessi, Elisabetta. TRAIL signalling regulation by ezrin : Régulation de la signalisation TRAIL par l'ezrine.

Degree: Docteur es, Sciences de la vie, 2011, Université de Bourgogne

URL: http://www.theses.fr/2011DIJOS055

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Objectifs: La cytokine TRAIL (TNF Related Apoptosis Inducing Ligand) suscite un intérêt majeur en thérapie anti-cancéreuse grâce à sa capacité à induire l’apoptose des cellules… (more)

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Objectifs: La cytokine TRAIL (TNF Related Apoptosis Inducing Ligand) suscite un intérêt majeur en thérapie anti-cancéreuse grâce à sa capacité à induire l’apoptose des cellules cancéreuses tout en épargnant les cellules saines. L’association du récepteur Fas et de l’actine via l’ezrine, une protéine de la famille ERM (Ezrin, Moesin, Radixin), régule les premières étapes de l’induction de l’apoptose par FasL. Au cours de mon projet de thèse, nous avons voulu déterminer le rôle que pouvait jouer l’ezrine au cours de l’apoptose induite par TRAIL, dans des lymphomes B ou des cellules cancéreuses adhérentes (HeLa, HCT116 et SW480). Matériel et Méthodes: Des approches biochimiques et moléculaires nous ont permis d’étudier et de déterminer l’implication de l’ezrine et sa phosphorylation dans la régulation de la mort induite par TRAIL. Résultats: Ce travail démontre que l’ezrine peut réguler de manière négative l’apoptose induite par TRAIL et FasL. Cette activité inhibitrice est régulée par la phosphorylation/déphosphorylation sur la serine 66 ainsi que sur la thréonine 353. Néanmoins cette régulation n’affecte ni la formation, ni l’activation du DISC (Death Inducing Signalling Complex). Des mutations de ces résidus par une alanine (S66A) ou un acide aspartique (Y353D) augmente sélectivement la capacité de TRAIL à induire l’apoptose. Au contraire, des mutations ponctuelles de ces résidus permettant de mimer la phosphorylation de l’ezrine sur la serine 66 (S66D) ou l’expression d’un variant non phosphorylable sur la thréonine 353 (Y353F) protègent les cellules cancéreuses de l’apoptose induite par TRAIL. De manière concordante, l’utilisation du H89, un inhibiteur de PKA, kinase responsable de la phosphorylation de la serine 66 augmente la sensibilité des cellules cancéreuses à TRAIL, alors qu’au contraire, un activateur de PKA (8bromocyclic AMP) rend ces mêmes cellules plus résistantes à TRAIL. Enfin, l’association de TRAIL et du cisplatine permet de dépasser l’inhibition de l’apoptose par l’ezrine.

Background and Aim: TRAIL has sparked a growing interest in oncology due to its ability to selectively trigger cancer cell death while sparing normal cells. The Fas/actin association through ezrin, a member of the ERM protein family, has been reported to regulate early steps of Fas-mediated apoptosis. In this project, we addressed the role of ezrin regarding TRAIL-induced cell death in B lymphoma cell lines, or adherent cancer cell lines (HeLa WT, HCT116, SW480). Methods: Molecular and biochemical approaches were employed to study the relevance of ezrin and its phosphorylation status in TRAIL signaling. Results: We found that ezrin displays a negative function towards TRAIL- and Fas-mediated apoptosis and that the ezrin-mediated TRAIL-induced cell death inhibition led to ezrin activation through phosphorylation/dephosphorylation events at serine 66 and tyrosine 353, but is mainly independent of TRAIL DISC (Death Inducing Signalling Complex) formation or activation. Mutations of these residues to alanine (S66A) or aspartic acid…

Advisors/Committee Members: Micheau, Olivier (thesis director), Solary, Éric (thesis director).

Subjects/Keywords: Cancer; TRAIL; TRAIL-R; Ezrine; Actine; Cytosquelette; Phosphorylation; Chimiothérapie; Cancer; TRAIL; TRAIL-R; Ezrin; Actin; Cytoskeleton; Phosphorylation; Chemotherapy; 572; 616.9

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Iessi, E. (2011). TRAIL signalling regulation by ezrin : Régulation de la signalisation TRAIL par l'ezrine. (Doctoral Dissertation). Université de Bourgogne. Retrieved from http://www.theses.fr/2011DIJOS055

Chicago Manual of Style (16^th Edition):

Iessi, Elisabetta. “TRAIL signalling regulation by ezrin : Régulation de la signalisation TRAIL par l'ezrine.” 2011. Doctoral Dissertation, Université de Bourgogne. Accessed January 16, 2021. http://www.theses.fr/2011DIJOS055.

MLA Handbook (7^th Edition):

Iessi, Elisabetta. “TRAIL signalling regulation by ezrin : Régulation de la signalisation TRAIL par l'ezrine.” 2011. Web. 16 Jan 2021.

Vancouver:

Iessi E. TRAIL signalling regulation by ezrin : Régulation de la signalisation TRAIL par l'ezrine. [Internet] [Doctoral dissertation]. Université de Bourgogne; 2011. [cited 2021 Jan 16]. Available from: http://www.theses.fr/2011DIJOS055.

Council of Science Editors:

Iessi E. TRAIL signalling regulation by ezrin : Régulation de la signalisation TRAIL par l'ezrine. [Doctoral Dissertation]. Université de Bourgogne; 2011. Available from: http://www.theses.fr/2011DIJOS055

Freie Universität Berlin

13. Shah, Maliha. Das Zytoskelett-Linker-Protein Ezrin hemmt a-Synuclein Fibrillenbildung und Toxizität durch einen neuartigen Wirkmechanismus.

Degree: 2014, Freie Universität Berlin

URL: https://refubium.fu-berlin.de/handle/fub188/12935

► α-Synuclein – ein Schlüsselprotein in der Parkinson Krankheit (PD) – bildet große unlösliche Ablagerungen bestehend aus Amyloidfibrillen. Diese sind toxisch und verursachen den Verlust von… (more)

▼ α-Synuclein – ein Schlüsselprotein in der Parkinson Krankheit (PD) – bildet große unlösliche Ablagerungen bestehend aus Amyloidfibrillen. Diese sind toxisch und verursachen den Verlust von dopaminergen Neuronen – ein Charakteristikum der PD. Manche Proteine (z.B. Hitzeschock-Proteine) interagieren mit α-Synuclein und verhindern dessen Aggregatbildung. Sie sind somit ein Ausgangspunkt für weiterführende therapeutische Untersuchungen. In dieser Arbeit wurde daher in einer Bibliothek bestehend aus 13.824 Proteinen nach Inhibitoren der α-Synuclein Fibrillenbildung gesucht. Nach mehreren sehr stringenten Screening-Runden wurde das Zytoskelettprotein Ezrin als ein Modulator mit dem höchsten Potential identifiziert. Dieses Potential wurde durch zahlreiche biophysikalische und biochemische Methoden einschließlich Rasterkraftmikroskopie, SDS-PAGE und in vitro Fibrillisierung überprüft. Außerdem wurde auch gezeigt, dass nahverwandte Mitglieder der Ezrin-Familie, als starke Fibrillisierungsmodulatoren wirken. Nuklear-Magnet-Resonanz (NMR) Spektroskopie wurde eingesetzt, um den neuartigen Wirkmechanismus von Ezrin bei der α-Synuclein Aggregation zu untersuchen. Es konnte gezeigt werden, dass Ezrin mit kleinen, krankheitsrelevanten α-Synuclein Oligomeren aber nicht mit Monomeren interagiert. Dies führt zur Bildung von off-pathway α-Synuclein Aggregaten, die sich strukturell von Fibrillen unterscheiden. Außerdem wurde in zellbasierten Versuchen mehrfach demonstriert, dass Ezrin die α-Synuclein vermittelte Toxizität auf primäre Neurone in Kultur signifikant verringern kann. Diese Ergebnisse wurden auch in einem Hefezellmodell erfolgreich bestätigt. Schließlich konnte auch durch Mikroskopie-Studien eine Abnahme von α-Synuclein Aggregaten in Ezrin co-exprimierenden Hefezellen gezeigt werden. Zusammenfassend kann gesagt werden, dass in dieser Arbeit ein neuartiger, sehr potenter α-Synuclein Fibrillisierungsinhibitor identifiziert wurde. Das Protein Ezrin wurde im Detail charakterisiert und die durchgeführten Untersuchungen lieferten wichtige Einblicke in den Mechanismus der spontanen α-Synuclein Aggregation. Gleichzeitig beweist die Arbeit durch Zell-basierte und in vivo Studien, dass Ezrin die Toxizität von α-Synuclein Aggregaten in Zellen reduzieren kann. Das Protein ist somit ein wichtiger neuer Ansatzpunkt für weiterführende therapeutische Studien. Des Weiteren führten die Untersuchungen der α-Synuclein Fibrillisierung mit Ezrin zu neuen Einblicken in die zellulären Regulations-mechanismen der α-Synuclein Fibrillenbildung in Zellen. Die Studien werfen ein neues Licht auf die Fehlregulation dieses Prozesses in PD Patienten und könnten längerfristig zu einem besseren Verständnis der Pathogenese bei PD führen. Da Ezrin verstärkt im gastro- intestinal Trakt exprimiert wird, einem Areal in dem viele Forscher den Ursprung der PD Pathologie vermuten, könnten weiterführende Studien zur Aufklärung der potentiellen Krankheitsmechanismen im Darm beitragen. Advisors/Committee Members: [email protected] (contact), w (gender), Prof. Dr. Erich E. Wanker (firstReferee), Prof. Dr. Fritz G. Rathjen (furtherReferee).

Subjects/Keywords: ezrin; alpha-synuclein; fibrillization; toxicity; aggregation; inhibition; mechanism; 500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::572 Biochemie

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shah, M. (2014). Das Zytoskelett-Linker-Protein Ezrin hemmt a-Synuclein Fibrillenbildung und Toxizität durch einen neuartigen Wirkmechanismus. (Thesis). Freie Universität Berlin. Retrieved from https://refubium.fu-berlin.de/handle/fub188/12935

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Shah, Maliha. “Das Zytoskelett-Linker-Protein Ezrin hemmt a-Synuclein Fibrillenbildung und Toxizität durch einen neuartigen Wirkmechanismus.” 2014. Thesis, Freie Universität Berlin. Accessed January 16, 2021. https://refubium.fu-berlin.de/handle/fub188/12935.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Shah, Maliha. “Das Zytoskelett-Linker-Protein Ezrin hemmt a-Synuclein Fibrillenbildung und Toxizität durch einen neuartigen Wirkmechanismus.” 2014. Web. 16 Jan 2021.

Vancouver:

Shah M. Das Zytoskelett-Linker-Protein Ezrin hemmt a-Synuclein Fibrillenbildung und Toxizität durch einen neuartigen Wirkmechanismus. [Internet] [Thesis]. Freie Universität Berlin; 2014. [cited 2021 Jan 16]. Available from: https://refubium.fu-berlin.de/handle/fub188/12935.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Shah M. Das Zytoskelett-Linker-Protein Ezrin hemmt a-Synuclein Fibrillenbildung und Toxizität durch einen neuartigen Wirkmechanismus. [Thesis]. Freie Universität Berlin; 2014. Available from: https://refubium.fu-berlin.de/handle/fub188/12935

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of St. Andrews

14. Herron, Lissa Rocha. A study of the behaviour and interactions of the novel FERM protein Willin .

Degree: 2008, University of St. Andrews

URL: http://hdl.handle.net/10023/418

► Willin is a novel member of the Four-point-one Ezrin Radixin Moesin (FERM) protein superfamily, containing an N-terminal FERM domain most like the Ezrin-Radixin-Moesin (ERM) family… (more)

Subjects/Keywords: Willin; FERM; Merlin; Ezrin; Radixin; Moesin; Neurofascin; L1

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Herron, L. R. (2008). A study of the behaviour and interactions of the novel FERM protein Willin . (Thesis). University of St. Andrews. Retrieved from http://hdl.handle.net/10023/418

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Herron, Lissa Rocha. “A study of the behaviour and interactions of the novel FERM protein Willin .” 2008. Thesis, University of St. Andrews. Accessed January 16, 2021. http://hdl.handle.net/10023/418.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Herron, Lissa Rocha. “A study of the behaviour and interactions of the novel FERM protein Willin .” 2008. Web. 16 Jan 2021.

Vancouver:

Herron LR. A study of the behaviour and interactions of the novel FERM protein Willin . [Internet] [Thesis]. University of St. Andrews; 2008. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10023/418.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Herron LR. A study of the behaviour and interactions of the novel FERM protein Willin . [Thesis]. University of St. Andrews; 2008. Available from: http://hdl.handle.net/10023/418

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

15. Zhang, Z. Protein-protein interactions involved in Rap1-mediated signal transduction.

Degree: 2007, University Utrecht

URL: https://dspace.library.uu.nl/handle/1874/19793 ; URN:NBN:NL:UI:10-1874-19793 ; urn:isbn:978-90-393-4444-6 ; URN:NBN:NL:UI:10-1874-19793 ; https://dspace.library.uu.nl/handle/1874/19793

► Signal transduction pathways play important roles in cell differentiation, proliferation, and survival. Specific protein-protein interactions mediate the assemblies of protein complexes in response to different… (more)

▼ Signal transduction pathways play important roles in cell differentiation, proliferation, and survival. Specific protein-protein interactions mediate the assemblies of protein complexes in response to different signals therefore regulate the proper transmission of cellular signals. Inappropriate protein-protein interactions within signalling pathways can lead to many diseases, including cancer. Proteomics-based approaches, which enable the quantitative investigation of protein-protein interactions involved in signalling networks, provide us with techniques to define the molecules controlling various signalling pathways. The small GTPase Rap1 belongs to the Ras family and shares high similarity with Ras protein. Rap1 cycles between an inactive GDP-bound state and an active GTP-bound state. This cycle is regulated by guanine nucleotide exchange factors (GEFs), such as Epac and GTPase activating proteins (GAPs), such as Rap1GAP. The most well-established processes where Rap1 is involved in include integrin-mediated adhesion and cadherin-mediated cell-cell adhesion. The GEFs are regulated by second messengers and are part of a protein-protein network, which regulates their temporal and spatial activities. The objective of the work described in this thesis was to investigate how Rap1 signaling pathway is regulated and to identify and characterize signaling proteins that direct the Rap1 pathway. In chapter 2, we studied the relation between AF6 and Rap1. We show that the overexpression of AF6 inhibits Rap1 induced adhesion. In addition, knocking-down the endogenous AF6 increases adhesion. These results show that in Jurkat T cells, AF6 functions to buffer GTP-Rap in resting cells and negatively regulates Rap1 function. In chapter 3 we analyze three Rap-like pseudogenes (mRap1A-retro1, mRap1A-retro2 and hRap1B-retro) in mouse and human genome. We show that all three retrogenes are expressed and encode functional proteins. These proteins appeared to stay more in a GTP-bound state compared to wild type Rap1. More interestingly, they exhibit clear differences in their ability to induce cell adhesion and spreading. To gain more insight in the protein interaction network, which controls the spatial and temporal organisation of Rap specific GEFs we performed yeast two-hybrid screens using Epac and PDZ-GEF as baits. This is described in chapter 4 addendum. A general summary of the results is given and candidate proteins were discussed. In chapter 4 and chapter 5 we characterized in detail the interaction between ERM (Ezrin-Radixin-Moesin) proteins and Epac1. We show that both Ezrin and Radixin interact with Epac1 in an activation-dependent manner. The Ezrin/Radixin binding region was identified in the N-terminus of Epac1. Furthermore, we demonstrate that this region is also required for the localization of Epac1 at microvilli in fully polarized cells. We show that Ezrin couples the activation of the ?-adrenergic receptor to Rap1 signalling via the recruitment of Epac1. In chapter 5 a novel Radixin mutant was characterized. This…

Subjects/Keywords: Rap; cancer; signal transduction; AF6; ezrin; adhesion

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhang, Z. (2007). Protein-protein interactions involved in Rap1-mediated signal transduction. (Doctoral Dissertation). University Utrecht. Retrieved from https://dspace.library.uu.nl/handle/1874/19793 ; URN:NBN:NL:UI:10-1874-19793 ; urn:isbn:978-90-393-4444-6 ; URN:NBN:NL:UI:10-1874-19793 ; https://dspace.library.uu.nl/handle/1874/19793

Chicago Manual of Style (16^th Edition):

Zhang, Z. “Protein-protein interactions involved in Rap1-mediated signal transduction.” 2007. Doctoral Dissertation, University Utrecht. Accessed January 16, 2021. https://dspace.library.uu.nl/handle/1874/19793 ; URN:NBN:NL:UI:10-1874-19793 ; urn:isbn:978-90-393-4444-6 ; URN:NBN:NL:UI:10-1874-19793 ; https://dspace.library.uu.nl/handle/1874/19793.

MLA Handbook (7^th Edition):

Zhang, Z. “Protein-protein interactions involved in Rap1-mediated signal transduction.” 2007. Web. 16 Jan 2021.

Vancouver:

Zhang Z. Protein-protein interactions involved in Rap1-mediated signal transduction. [Internet] [Doctoral dissertation]. University Utrecht; 2007. [cited 2021 Jan 16]. Available from: https://dspace.library.uu.nl/handle/1874/19793 ; URN:NBN:NL:UI:10-1874-19793 ; urn:isbn:978-90-393-4444-6 ; URN:NBN:NL:UI:10-1874-19793 ; https://dspace.library.uu.nl/handle/1874/19793.

Council of Science Editors:

Zhang Z. Protein-protein interactions involved in Rap1-mediated signal transduction. [Doctoral Dissertation]. University Utrecht; 2007. Available from: https://dspace.library.uu.nl/handle/1874/19793 ; URN:NBN:NL:UI:10-1874-19793 ; urn:isbn:978-90-393-4444-6 ; URN:NBN:NL:UI:10-1874-19793 ; https://dspace.library.uu.nl/handle/1874/19793

Université Paris-Sud – Paris XI

16. Rayah, Amel. Identification des voies biochimiques stimulées par le récepteur purinergique P2X7 qui sont impliquées dans le clivage protéolytique du précurseur de la protéine amyloïde (APP) : Identification of the Biochemical Pathways Stimulated by Purinergic Receptor P2X7 Involved in the Proteolytic Clivage of the Amyloid Precursor Protein (APP).

Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2015, Université Paris-Sud – Paris XI

URL: http://www.theses.fr/2015PA11T043

►

Le précurseur de la protéine amyloïde (APP) est une protéine transmembranaire qui, après coupure séquentielle par les sécrétases β et γ, produit des peptides Aβ… (more)

▼

Le précurseur de la protéine amyloïde (APP) est une protéine transmembranaire qui, après coupure séquentielle par les sécrétases β et γ, produit des peptides Aβ trouvés dans les plaques séniles de patientsatteints d’Alzheimer. Par contre, la forme soluble de l’APP (sAPPα), produite après coupure par une sécrétase α, augmente la survie cellulaire, la croissance des neurites et la synaptogénèse. L’APP est coupéeau site α par 3 métalloprotéases : ADAM9, ADAM10 et ADAM17.Notre laboratoire a montré que la stimulation du récepteur purinergique P2X7 (P2X7R) provoque la coupure protéolytique du précurseur de la protéine amyloïde (APP). Le Dr Delarasse a établi que la voie non amyloïdogénique est mise en jeu et que c'est le fragment sAPPα, neuroprotecteur, qui est produit. Deplus, le laboratoire a précédemment démontré que ce ne sont pas les alpha-sécrétases ADAM9, 10 et 17 qui sont responsables du clivage protéolytique de l'APP après stimulation du P2X7R dans les cellules de neuroblastome Neuro2a.Durant mes travaux de thèse, nous avons étudié la voie biochimique menant à la libération du fragments APPα. L’activation du P2X7R stimule la phosphorylation et la translocation rapide à la membrane plasmique de protéines, appelées ezrine, radixine et moesine (ERM) qui ont la capacité d’établir un lien entre la région cytosolique du P2X7R et la F-actine. Les ERM jouent un rôle crucial dans la coupure protéolytique de l’APP par les métalloprotéases ADAM. En effet, l’inhibition de l’expression des ERM par RNA interférence aboutit à une absence de coupure de l’APP. Par ailleurs, nous avons observé que les MAPKERK1/2 et JNK et la ROCKinase sont nécessaires à la phosphorylation activatrice des ERM et jouent donc un rôle en amont des ERM. Enfin, nous avons mis en évidence le rôle de la PI3K en aval des ERM.Par ailleurs, nous avons démontré que l’activation du récepteur purinergique P2X7 entraînait la coupure protéolytique de la molécule NrCAM par ADAM17 aboutissant à la libération du fragment soluble del’ectodomaine de NrCAM. Les résultats obtenus indiquent que la coupure de NrCAM est dépendante de l’activation et de la fixation des ERM à NrCAM. Ces résultats suggèrent fortement que les ERM sont indispensables à la coupure protéolytique de différents substrats après stimulation du P2X7R.Les données obtenues mettent en évidence un mécanisme moléculaire original et important qui fait jouer aux ERM un rôle central de « liens moléculaires » dans le clivage protéolytique des protéines transmembranaires. A ce stade de notre étude, nous émettons l’hypothèse que les ERM agissent en aval du récepteur P2X7, en liant les substrats et/ou les protéases qu’ils regroupent à la membrane plasmique favorisant ainsi le clivage des substrats.

The amyloid protein precursor (APP) can be cleaved in neural cells by α-secretases to produce the soluble APP ectodomain (sAPPα), which is neuroprotective. We have shown previously that activation of the purinergic receptor P2X7 (P2X7R), a member of the P2X receptor family of ATP-gated cation channels, triggers sAPPα…

Advisors/Committee Members: Kanellopoulos, Jean (thesis director).

Subjects/Keywords: APP; P2X7; Ezrine Radixine Moesine; ATP; Maladie d'Alzheimer; ERM; APP; P2X7; Ezrin Radixin Moesin; ATP; Alzheimer disease; ERM

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rayah, A. (2015). Identification des voies biochimiques stimulées par le récepteur purinergique P2X7 qui sont impliquées dans le clivage protéolytique du précurseur de la protéine amyloïde (APP) : Identification of the Biochemical Pathways Stimulated by Purinergic Receptor P2X7 Involved in the Proteolytic Clivage of the Amyloid Precursor Protein (APP). (Doctoral Dissertation). Université Paris-Sud – Paris XI. Retrieved from http://www.theses.fr/2015PA11T043

Chicago Manual of Style (16^th Edition):

Rayah, Amel. “Identification des voies biochimiques stimulées par le récepteur purinergique P2X7 qui sont impliquées dans le clivage protéolytique du précurseur de la protéine amyloïde (APP) : Identification of the Biochemical Pathways Stimulated by Purinergic Receptor P2X7 Involved in the Proteolytic Clivage of the Amyloid Precursor Protein (APP).” 2015. Doctoral Dissertation, Université Paris-Sud – Paris XI. Accessed January 16, 2021. http://www.theses.fr/2015PA11T043.

MLA Handbook (7^th Edition):

Rayah, Amel. “Identification des voies biochimiques stimulées par le récepteur purinergique P2X7 qui sont impliquées dans le clivage protéolytique du précurseur de la protéine amyloïde (APP) : Identification of the Biochemical Pathways Stimulated by Purinergic Receptor P2X7 Involved in the Proteolytic Clivage of the Amyloid Precursor Protein (APP).” 2015. Web. 16 Jan 2021.

Vancouver:

Rayah A. Identification des voies biochimiques stimulées par le récepteur purinergique P2X7 qui sont impliquées dans le clivage protéolytique du précurseur de la protéine amyloïde (APP) : Identification of the Biochemical Pathways Stimulated by Purinergic Receptor P2X7 Involved in the Proteolytic Clivage of the Amyloid Precursor Protein (APP). [Internet] [Doctoral dissertation]. Université Paris-Sud – Paris XI; 2015. [cited 2021 Jan 16]. Available from: http://www.theses.fr/2015PA11T043.

Council of Science Editors:

Rayah A. Identification des voies biochimiques stimulées par le récepteur purinergique P2X7 qui sont impliquées dans le clivage protéolytique du précurseur de la protéine amyloïde (APP) : Identification of the Biochemical Pathways Stimulated by Purinergic Receptor P2X7 Involved in the Proteolytic Clivage of the Amyloid Precursor Protein (APP). [Doctoral Dissertation]. Université Paris-Sud – Paris XI; 2015. Available from: http://www.theses.fr/2015PA11T043

17. Zhao, Jun. Subcellular localisation of Epac.

Degree: 2006, University Utrecht

URL: https://dspace.library.uu.nl/handle/1874/12552 ; URN:NBN:NL:UI:10-1874-12552 ; 1874/12552 ; urn:isbn:9039343276 ; URN:NBN:NL:UI:10-1874-12552 ; https://dspace.library.uu.nl/handle/1874/12552

► Cyclic adenosine 3', 5'- monophosphate (cAMP) is a second messenger that functions through binding to its downstream targets protein kinase A (PKA), cyclic-regulated ion channels… (more)

▼ Cyclic adenosine 3', 5'- monophosphate (cAMP) is a second messenger that functions through binding to its downstream targets protein kinase A (PKA), cyclic-regulated ion channels (CNG channels) and Epac1 (exchange protein directly activated by cAMP). Epac1 is guanine nucleotide exchange factor toward both Rap1 and Rap2. It is kept in the inactive conformation by an intramolecular interaction between the regulatory and catalytic domain. Binding of cAMP to the cAMP binding domain liberates the catalytic domain, resulting in the activation of Epac. In order to visualize the conformational change between inactivate- and active- state of Epac, a CFP-Epac-YFP probe was generated and fluorescence resonance energy transfer (FRET) between the two fluorescent moieties was monitored in vivo. The FRET signal was rapidly decreased in response to cAMP-raising agents, whereas it fully recovers after addition of cAMP-lowering agonists. This indicates that cAMP causes a significant conformational change in vivo and supports the unfolding model for Epac1 activation. To unravel more functions of Epac1, a series of Epac1 antibodies (Abs) were generated and characterized. 5D3, one of Epac1 monoclonal Abs, was further characterized based on its ability to recognize activate conformation Epac1. In vitro, the epitope of 5D3 was mapped within the cAMP binding domain, especially around Leucine 273. This region is hidden during autoinhibition. Using Epac1 Abs, subcellular localization of Epac1 was investigated in detail. Epac1 is mainly distributed around perinuclear region, especially in the endoplasmatic reticulum and the Golgi apparatus, as well as in the plasma membrane, especially at microvilli in fully polarized cells. Functional domains which are responsible for proper localization of Epac1 were also analyzed in detail. Our results revealed that both DEP domain and the EzB domain (the first 49 aa) are required for correct localization of Epac1 and the activation of Rap. The EzB domain is not only responsible but also sufficient for targeting Epac1 at microvilli. In contrast the DEP domain is only responsible for membrane localisation. Importantly, the microvillar localization is through binding to Ezrin/Radixin, proteins that function as linkers between the actin cytoskeleton and the apical membrane of polarized cells and as scaffold protein for protein complexes. The functional relevance of this interaction is still unclear, but the mere fact that Epac1 only binds to the active form of Ezrin/Radixin indicates that activation of these proteins is a crucial step in the spatial regulation of Epac1. Nuclear accumulation of Epac was also observed after removing the EzB domain. This effect could be mimicked by stimulation of the cells with HGF, that induces cell scattering, and with overexpression of RapV12 that induces cell spreading. These results suggest that upon loss of cell polarity and thus disruption of the apical structures, part of Epac1 translocation to the nucleus. However, the function of Epac1 in the nucleus remains a question…

Subjects/Keywords: Epac; FRET probe; epitope mapping; Ezrin; microvilli

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhao, J. (2006). Subcellular localisation of Epac. (Doctoral Dissertation). University Utrecht. Retrieved from https://dspace.library.uu.nl/handle/1874/12552 ; URN:NBN:NL:UI:10-1874-12552 ; 1874/12552 ; urn:isbn:9039343276 ; URN:NBN:NL:UI:10-1874-12552 ; https://dspace.library.uu.nl/handle/1874/12552

Chicago Manual of Style (16^th Edition):

Zhao, Jun. “Subcellular localisation of Epac.” 2006. Doctoral Dissertation, University Utrecht. Accessed January 16, 2021. https://dspace.library.uu.nl/handle/1874/12552 ; URN:NBN:NL:UI:10-1874-12552 ; 1874/12552 ; urn:isbn:9039343276 ; URN:NBN:NL:UI:10-1874-12552 ; https://dspace.library.uu.nl/handle/1874/12552.

MLA Handbook (7^th Edition):

Zhao, Jun. “Subcellular localisation of Epac.” 2006. Web. 16 Jan 2021.

Vancouver:

Zhao J. Subcellular localisation of Epac. [Internet] [Doctoral dissertation]. University Utrecht; 2006. [cited 2021 Jan 16]. Available from: https://dspace.library.uu.nl/handle/1874/12552 ; URN:NBN:NL:UI:10-1874-12552 ; 1874/12552 ; urn:isbn:9039343276 ; URN:NBN:NL:UI:10-1874-12552 ; https://dspace.library.uu.nl/handle/1874/12552.

Council of Science Editors:

Zhao J. Subcellular localisation of Epac. [Doctoral Dissertation]. University Utrecht; 2006. Available from: https://dspace.library.uu.nl/handle/1874/12552 ; URN:NBN:NL:UI:10-1874-12552 ; 1874/12552 ; urn:isbn:9039343276 ; URN:NBN:NL:UI:10-1874-12552 ; https://dspace.library.uu.nl/handle/1874/12552

18. Zhang, Z. Protein-protein interactions involved in Rap1-mediated signal transduction.

Degree: 2007, University Utrecht

URL: https://dspace.library.uu.nl/handle/1874/19793 ; URN:NBN:NL:UI:10-1874-19793 ; 1874/19793 ; urn:isbn:9789039344446 ; URN:NBN:NL:UI:10-1874-19793 ; https://dspace.library.uu.nl/handle/1874/19793

► Signal transduction pathways play important roles in cell differentiation, proliferation, and survival. Specific protein-protein interactions mediate the assemblies of protein complexes in response to different… (more)

▼ Signal transduction pathways play important roles in cell differentiation, proliferation, and survival. Specific protein-protein interactions mediate the assemblies of protein complexes in response to different signals therefore regulate the proper transmission of cellular signals. Inappropriate protein-protein interactions within signalling pathways can lead to many diseases, including cancer. Proteomics-based approaches, which enable the quantitative investigation of protein-protein interactions involved in signalling networks, provide us with techniques to define the molecules controlling various signalling pathways. The small GTPase Rap1 belongs to the Ras family and shares high similarity with Ras protein. Rap1 cycles between an inactive GDP-bound state and an active GTP-bound state. This cycle is regulated by guanine nucleotide exchange factors (GEFs), such as Epac and GTPase activating proteins (GAPs), such as Rap1GAP. The most well-established processes where Rap1 is involved in include integrin-mediated adhesion and cadherin-mediated cell-cell adhesion. The GEFs are regulated by second messengers and are part of a protein-protein network, which regulates their temporal and spatial activities. The objective of the work described in this thesis was to investigate how Rap1 signaling pathway is regulated and to identify and characterize signaling proteins that direct the Rap1 pathway. In chapter 2, we studied the relation between AF6 and Rap1. We show that the overexpression of AF6 inhibits Rap1 induced adhesion. In addition, knocking-down the endogenous AF6 increases adhesion. These results show that in Jurkat T cells, AF6 functions to buffer GTP-Rap in resting cells and negatively regulates Rap1 function. In chapter 3 we analyze three Rap-like pseudogenes (mRap1A-retro1, mRap1A-retro2 and hRap1B-retro) in mouse and human genome. We show that all three retrogenes are expressed and encode functional proteins. These proteins appeared to stay more in a GTP-bound state compared to wild type Rap1. More interestingly, they exhibit clear differences in their ability to induce cell adhesion and spreading. To gain more insight in the protein interaction network, which controls the spatial and temporal organisation of Rap specific GEFs we performed yeast two-hybrid screens using Epac and PDZ-GEF as baits. This is described in chapter 4 addendum. A general summary of the results is given and candidate proteins were discussed. In chapter 4 and chapter 5 we characterized in detail the interaction between ERM (Ezrin-Radixin-Moesin) proteins and Epac1. We show that both Ezrin and Radixin interact with Epac1 in an activation-dependent manner. The Ezrin/Radixin binding region was identified in the N-terminus of Epac1. Furthermore, we demonstrate that this region is also required for the localization of Epac1 at microvilli in fully polarized cells. We show that Ezrin couples the activation of the ?-adrenergic receptor to Rap1 signalling via the recruitment of Epac1. In chapter 5 a novel Radixin mutant was characterized. This…

Subjects/Keywords: Rap; cancer; signal transduction; AF6; ezrin; adhesion

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APA (6^th Edition):

Zhang, Z. (2007). Protein-protein interactions involved in Rap1-mediated signal transduction. (Doctoral Dissertation). University Utrecht. Retrieved from https://dspace.library.uu.nl/handle/1874/19793 ; URN:NBN:NL:UI:10-1874-19793 ; 1874/19793 ; urn:isbn:9789039344446 ; URN:NBN:NL:UI:10-1874-19793 ; https://dspace.library.uu.nl/handle/1874/19793

Chicago Manual of Style (16^th Edition):

Zhang, Z. “Protein-protein interactions involved in Rap1-mediated signal transduction.” 2007. Doctoral Dissertation, University Utrecht. Accessed January 16, 2021. https://dspace.library.uu.nl/handle/1874/19793 ; URN:NBN:NL:UI:10-1874-19793 ; 1874/19793 ; urn:isbn:9789039344446 ; URN:NBN:NL:UI:10-1874-19793 ; https://dspace.library.uu.nl/handle/1874/19793.

MLA Handbook (7^th Edition):

Zhang, Z. “Protein-protein interactions involved in Rap1-mediated signal transduction.” 2007. Web. 16 Jan 2021.

Vancouver:

Zhang Z. Protein-protein interactions involved in Rap1-mediated signal transduction. [Internet] [Doctoral dissertation]. University Utrecht; 2007. [cited 2021 Jan 16]. Available from: https://dspace.library.uu.nl/handle/1874/19793 ; URN:NBN:NL:UI:10-1874-19793 ; 1874/19793 ; urn:isbn:9789039344446 ; URN:NBN:NL:UI:10-1874-19793 ; https://dspace.library.uu.nl/handle/1874/19793.

Council of Science Editors:

Zhang Z. Protein-protein interactions involved in Rap1-mediated signal transduction. [Doctoral Dissertation]. University Utrecht; 2007. Available from: https://dspace.library.uu.nl/handle/1874/19793 ; URN:NBN:NL:UI:10-1874-19793 ; 1874/19793 ; urn:isbn:9789039344446 ; URN:NBN:NL:UI:10-1874-19793 ; https://dspace.library.uu.nl/handle/1874/19793

19. Persson, Åsa. Induction of the cytoskeletal protein radixin in the adult brain.

Degree: 2012, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/30264

► Abstract Neural stem and progenitor cells (NSPCs) proliferate throughout life in two regions of the brain, namely the subventricular zone (SVZ) of the lateral ventricles… (more)

▼ Abstract Neural stem and progenitor cells (NSPCs) proliferate throughout life in two regions of the brain, namely the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of dentate gyrus in the hippocampus. In the adult SVZ, NSPCs give rise to neuroblasts that leave the SVZ for long distance migration along the rostral migratory stream (RMS), on their way to the olfactory bulb where they mature and are integrated in the neural network. Understanding how adult neuronal migration is regulated is of importance for the development of new therapeutic interventions using endogenous stem or progenitor cells for brain repair strategies. Long distance migration of neuroblasts in the RMS requires a highly dynamic cytoskeleton with the ability to respond to surrounding stimuli. In this thesis, we hypothesized that cytoskeleton rearrangement in the RMS is mediated by the ERM (Ezrin/Radixin/Moesin) family of proteins. ERM proteins regulate actin polymerization through interaction with actin and transmembrane adhesion molecules in many different parts of the body, however, limited studies exist of ERM proteins in the adult brain. In the first paper, our studies demonstrate the specific expression of radixin in neuroblasts in both the ventricular and hippocampal neurogenic niches. We also demonstrate the presence of radixin in Olig2 expressing cells throughout the adult brain. In the second study, the function of radixin was inhibited using a selective quinocarmycin analog which interrupts the ability for radixin to link the actin cytoskeleton to the membrane. Inhibition of radixin in SVZ explant cultures selectively blocked the migration of neuroblasts, whereas glial migration remained unaltered, suggesting that these populations use different ERM proteins for actin polymerization. In addition, intracerebroventricular infusion of the radixin inhibitor resulted in aberrant neuroblast chain formation and decreased neuroblast proliferation in the RMS. In the third paper, EGF infusion revealed elevated levels of radixin expression in the SVZ and RMS. EGF treatment is known to greatly reduce the migratory population in the SVZ and RMS. Accordingly, a new radixin expressing population was present in the RMS after EGF treatment and these cells also expressed Olig2. Proliferation of the radixin/Olig2+ population occurred already after 24h, even in parts of the RMS that are distal to the SVZ, suggesting local activation by EGF throughout the RMS rather than migration from the SVZ. The radixin/Olig2+ cells in the RMS were arranged in chains and migrated in explant cultures in vitro. Being negative for NG2 and CNPase, these radixin/Olig2+ cells are likely not oligodendrocyte progenitors. In the fourth study, radixin expression was induced in the peri-infarct region after cortical stroke. Unexpectedly, the number of cortical radixin/Olig2+ cells decreased after stroke and radixin was instead present in a subpopulation of activated microglia. In the healthy brain and in the contralateral cortex, microglia did not…

Subjects/Keywords: Rostral migratory stream; stroke; Neural stem cells; microglia; ezrin/radixin/moesin; Olig2

…28 The cytoskeletal proteins of the Ezrin/Radixin/Moesin family… …33 Ezrin expression in astrocytes in the RMS… …45 Expression of moesin and ezrin in the SVZ and RMS…

6 more images…

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APA (6^th Edition):

Persson, �. (2012). Induction of the cytoskeletal protein radixin in the adult brain. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/30264

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Persson, Åsa. “Induction of the cytoskeletal protein radixin in the adult brain.” 2012. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed January 16, 2021. http://hdl.handle.net/2077/30264.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Persson, Åsa. “Induction of the cytoskeletal protein radixin in the adult brain.” 2012. Web. 16 Jan 2021.

Vancouver:

Persson �. Induction of the cytoskeletal protein radixin in the adult brain. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2012. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/2077/30264.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Persson �. Induction of the cytoskeletal protein radixin in the adult brain. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2012. Available from: http://hdl.handle.net/2077/30264

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

20. Lubart, Quentin. Les protéines ERM , Interactions entre la membrane cellulaire et le cytosquelette : une approche biomimétique. : Interactions between ERM proteins, cell membrane and cytoskeleton : a biomimetic approach.

Degree: Docteur es, Matériaux, Mécanique, Génie civil, Electrochimie, 2016, Université Grenoble Alpes (ComUE)

URL: http://www.theses.fr/2016GREAI108

►

Les protéines ERMs (Ezrine, radixine et moésine) jouent un rôle central in cellulo, dans de nombreux processus cellulaires tels que les infections, la migration et… (more)

▼

Les protéines ERMs (Ezrine, radixine et moésine) jouent un rôle central in cellulo, dans de nombreux processus cellulaires tels que les infections, la migration et la division cellulaire. Parmi celles-ci, la moésine est plus particulièrement impliquée dans la formation de la synapse immunologique, l’infection virale et bactérienne, et les métastases cancéreuses. D’un point de vue structural, les ERM peuvent être en conformation inactive (replies sur elles-mêmes) ou actives (ouvertes), ce qui permet leur interaction a la fois avec les constituants du cytosquelette (actine et tubuline) via leur domaine C-terminal et la membrane plasmique via leur domaine FERM. La liaison a la membrane plasmique se fait principalement et spécifiquement via un lipide de la famille des phosphoinositides, le phosphatidyl 4,5 bisphosphate (PIP2). De plus, les protéines peuvent être phosphorylées, ce qui contribue à leur ouverture structurale. Cependant, le rôle de la phosphorylation sur les interactions ERM/membrane et ERM/cytosquelette, bien que beaucoup étudié in cellulo, est peu compris au niveau moléculaire.Le but de cette thèse est précisément d’étudier, au niveau moléculaire et à l’aide de systèmes biomimétiques, les interactions entre des protéines recombinantes et des membranes biomimétiques contenant du PIP2. Pour cela, nous avons mis au point des membranes lipidiques sous forme de vésicules unilamellaires (petites ou larges) et de bicouches lipidiques supportées, qui permettent de caractériser les interactions entre protéines et membranes par des techniques biophysiques complémentaires, notamment la cosédimentation quantitative, la microscopie et spectroscopie de fluorescence, et la microbalance à cristal de quartz. Dans une première partie, nous avons étudié le rôle de la double phosphorylation de la moésine (réalisée par mutation sur site spécifique) sur les interactions moésine/membrane biomimétique, en comparaison de la protéine sauvage, les protéines recombinantes et les mutants ayant été produites et purifiées au laboratoire.Nos résultats mettent en évidence une interaction spécifique et coopérative pour le double mutant phosphomimétique alors que cette interaction est simple dans le cas de la protéine sauvage. Dans une seconde partie, nous avons employé les bicouches lipidiques supportées contenant le PIP2 pour étudier les mécanismes molécules d’adsorption de la protéine virale Gag et de ses mutants. Les méthodologies développées dans ce travail de thèse ouvrent des perspectives en biophysique moléculaires car elles sont facilement transposables à l’étude d’autres protéines sur des membranes lipidiques modèles contenant des phosphoinositides.Mots clés: Ezrine-Radixine-Moésine, phosphoinositides, PIP2, interactions protéine-lipide, membrane lipidique biomimétique, protéine virale Gag, cytosquelette.

ERM (ezrin, radixin, moesin) proteins play a central role in cellulo in a large number of physiological and pathological processes, including cell infection, migration and cell division. Among the ERMs, moesin is particularly…

Advisors/Committee Members: Picart, Catherine (thesis director), Blanchoin, Laurent (thesis director).

Subjects/Keywords: Ezrine-Radixine-Moésine; Phosphoinositides et PIP2; Cytosquelette; Membrane lipidique biomimétique; Protéine virale Gag; Interactions protéine-Lipide; Ezrin-Radixin-Moesin; Phosphoinositides and PIP2; Cytosqueleton; Biomimetic lipidic membranes; Viral Gag protein; Interaction protein-Lipid; 570

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lubart, Q. (2016). Les protéines ERM , Interactions entre la membrane cellulaire et le cytosquelette : une approche biomimétique. : Interactions between ERM proteins, cell membrane and cytoskeleton : a biomimetic approach. (Doctoral Dissertation). Université Grenoble Alpes (ComUE). Retrieved from http://www.theses.fr/2016GREAI108

Chicago Manual of Style (16^th Edition):

Lubart, Quentin. “Les protéines ERM , Interactions entre la membrane cellulaire et le cytosquelette : une approche biomimétique. : Interactions between ERM proteins, cell membrane and cytoskeleton : a biomimetic approach.” 2016. Doctoral Dissertation, Université Grenoble Alpes (ComUE). Accessed January 16, 2021. http://www.theses.fr/2016GREAI108.

MLA Handbook (7^th Edition):

Lubart, Quentin. “Les protéines ERM , Interactions entre la membrane cellulaire et le cytosquelette : une approche biomimétique. : Interactions between ERM proteins, cell membrane and cytoskeleton : a biomimetic approach.” 2016. Web. 16 Jan 2021.

Vancouver:

Lubart Q. Les protéines ERM , Interactions entre la membrane cellulaire et le cytosquelette : une approche biomimétique. : Interactions between ERM proteins, cell membrane and cytoskeleton : a biomimetic approach. [Internet] [Doctoral dissertation]. Université Grenoble Alpes (ComUE); 2016. [cited 2021 Jan 16]. Available from: http://www.theses.fr/2016GREAI108.

Council of Science Editors:

Lubart Q. Les protéines ERM , Interactions entre la membrane cellulaire et le cytosquelette : une approche biomimétique. : Interactions between ERM proteins, cell membrane and cytoskeleton : a biomimetic approach. [Doctoral Dissertation]. Université Grenoble Alpes (ComUE); 2016. Available from: http://www.theses.fr/2016GREAI108

University of Lund

21. Jörgren, Fredrik. Risk Factors of Tumour Recurrence and Reduced Survival in Rectal Cancer.

Degree: 2010, University of Lund

URL: https://lup.lub.lu.se/record/1666691 ; https://portal.research.lu.se/ws/files/3826421/1666692.pdf

► In Sweden, 2000 patients are diagnosed with rectal cancer annually. In 1995, the Swedish Rectal Cancer Registry (SRCR) was launched to supervise and assure the… (more)

Subjects/Keywords: Surgery; Tumour Marker; Ezrin; Intestinal Perforation; Neoplasm Recurrence; Rectal Neoplasms; Local; Neoplasm Metastasis; Survival Rate; Risk Factors; Surgical; Anastomosis

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APA (6^th Edition):

Jörgren, F. (2010). Risk Factors of Tumour Recurrence and Reduced Survival in Rectal Cancer. (Doctoral Dissertation). University of Lund. Retrieved from https://lup.lub.lu.se/record/1666691 ; https://portal.research.lu.se/ws/files/3826421/1666692.pdf

Chicago Manual of Style (16^th Edition):

Jörgren, Fredrik. “Risk Factors of Tumour Recurrence and Reduced Survival in Rectal Cancer.” 2010. Doctoral Dissertation, University of Lund. Accessed January 16, 2021. https://lup.lub.lu.se/record/1666691 ; https://portal.research.lu.se/ws/files/3826421/1666692.pdf.

MLA Handbook (7^th Edition):

Jörgren, Fredrik. “Risk Factors of Tumour Recurrence and Reduced Survival in Rectal Cancer.” 2010. Web. 16 Jan 2021.

Vancouver:

Jörgren F. Risk Factors of Tumour Recurrence and Reduced Survival in Rectal Cancer. [Internet] [Doctoral dissertation]. University of Lund; 2010. [cited 2021 Jan 16]. Available from: https://lup.lub.lu.se/record/1666691 ; https://portal.research.lu.se/ws/files/3826421/1666692.pdf.

Council of Science Editors:

Jörgren F. Risk Factors of Tumour Recurrence and Reduced Survival in Rectal Cancer. [Doctoral Dissertation]. University of Lund; 2010. Available from: https://lup.lub.lu.se/record/1666691 ; https://portal.research.lu.se/ws/files/3826421/1666692.pdf

Kent State University

22. Sizemore, Steven T. The Role of Podocalyxin in Breast and Prostate Cancer Aggressiveness.

Degree: PhD, College of Arts and Sciences / School of Biomedical Sciences, 2008, Kent State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=kent1222799328

► Podocalyxin is an anti-adhesive transmembrane sialomucin that has been implicated in the development of more aggressive forms of breast and prostate cancer. The overall… (more)

Subjects/Keywords: Biomedical Research; podocalyxin; ezrin; breast cancer; prostate cancer; cancer aggressiveness; metastasis; akt; pi3k; mapk; invasion; migration

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APA (6^th Edition):

Sizemore, S. T. (2008). The Role of Podocalyxin in Breast and Prostate Cancer Aggressiveness. (Doctoral Dissertation). Kent State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=kent1222799328

Chicago Manual of Style (16^th Edition):

Sizemore, Steven T. “The Role of Podocalyxin in Breast and Prostate Cancer Aggressiveness.” 2008. Doctoral Dissertation, Kent State University. Accessed January 16, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=kent1222799328.

MLA Handbook (7^th Edition):

Sizemore, Steven T. “The Role of Podocalyxin in Breast and Prostate Cancer Aggressiveness.” 2008. Web. 16 Jan 2021.

Vancouver:

Sizemore ST. The Role of Podocalyxin in Breast and Prostate Cancer Aggressiveness. [Internet] [Doctoral dissertation]. Kent State University; 2008. [cited 2021 Jan 16]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=kent1222799328.

Council of Science Editors:

Sizemore ST. The Role of Podocalyxin in Breast and Prostate Cancer Aggressiveness. [Doctoral Dissertation]. Kent State University; 2008. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=kent1222799328

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Open Access Theses and Dissertations