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You searched for +publisher:"University of North Carolina" +contributor:("Black, Justin"). One record found.

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University of North Carolina

1. Black, Justin. Exploration of the role of CIB1 in cell survival and tumor growth.

Degree: Biochemistry and Biophysics, 2015, University of North Carolina

CIB1 is an intracellular protein with diverse functions in cancer cell biology. Here I explore two important functions of CIB1: 1) The role of CIB1 in cell survival and tumor growth in triple negative breast cancer; and 2) The interaction between CIB1 and α-integrin cytoplasmic tails and the role of this interaction in cell biology. Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype with an unmet need for novel targeted therapeutics. We previously demonstrated that CIB1 is necessary for cancer cell survival and proliferation via regulation of two oncogenic signaling pathways, RAS-RAF-MEK-ERK and PI3K-AKT. Because these pathways are often upregulated in TNBC, we hypothesized that CIB1 may play a broader role in TNBC cell survival and tumor growth. Here we find that CIB1 is necessary for cell survival in multiple TNBC cell lines in vitro, and TNBC xenograft tumor growth in vivo. Furthermore, elevated AKT activation status and low PTEN expression were key predictors of sensitivity to CIB1 depletion in TNBC cells. Importantly, CIB1 knockdown caused dramatic shrinkage of MDA-MB-468 xenograft tumors in vivo. RNA sequence analysis showed that CIB1 depletion activates gene programs associated with decreased proliferation and increased cell death. Taken together, our data are consistent with the emerging theory of non-oncogene addiction, where a large subset of TNBCs depend on CIB1 for cell survival and tumor growth, independent of CIB1 expression levels. Integrins are heterodimeric transmembrane receptors important for cell adhesion to the extracellular matrix and transmission of signals through the cell membrane. Integrins are regulated via binding of cytoplasmic proteins to the integrin cytoplasmic tail. CIB1 was discovered as a binding partner of one integrin, αIIb, but the role of CIB1 in binding and regulating additional integrins was previously unknown. Here I also present evidence that CIB1 interacts with integrin αV via residues in the transmembrane portion of the integrin, can access these residues in the presence of a cell membrane, and that CIB1-integrin binding may contribute to cell signaling and proliferation. In summary, CIB1 is a diverse protein with important functions in TNBC cell survival and proliferation, as well as integrin biology. Advisors/Committee Members: Black, Justin, Parise, Leslie, Bergmeier, Wolfgang, Campbell, Sharon, Burridge, Keith, Hahn, Klaus.

Subjects/Keywords: Biochemistry; Cytology; Genetics; School of Medicine; Department of Biochemistry and Biophysics

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

APA (6th Edition):

Black, J. (2015). Exploration of the role of CIB1 in cell survival and tumor growth. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:b58ffcb6-4707-43a6-b86e-4644085f46e1

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

Chicago Manual of Style (16th Edition):

Black, Justin. “Exploration of the role of CIB1 in cell survival and tumor growth.” 2015. Thesis, University of North Carolina. Accessed December 05, 2020. https://cdr.lib.unc.edu/record/uuid:b58ffcb6-4707-43a6-b86e-4644085f46e1.

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

MLA Handbook (7th Edition):

Black, Justin. “Exploration of the role of CIB1 in cell survival and tumor growth.” 2015. Web. 05 Dec 2020.

Vancouver:

Black J. Exploration of the role of CIB1 in cell survival and tumor growth. [Internet] [Thesis]. University of North Carolina; 2015. [cited 2020 Dec 05]. Available from: https://cdr.lib.unc.edu/record/uuid:b58ffcb6-4707-43a6-b86e-4644085f46e1.

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

Council of Science Editors:

Black J. Exploration of the role of CIB1 in cell survival and tumor growth. [Thesis]. University of North Carolina; 2015. Available from: https://cdr.lib.unc.edu/record/uuid:b58ffcb6-4707-43a6-b86e-4644085f46e1

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

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