THE ROLE OF INTEGRIN-SWITCHING AND DEPTOR IN ONCOGENIC TGF-B SIGNALING AND BREAST CANCER METASTASIS

Bibliographic Details
Main Author:	Parvani, Jenny G.
Language:	English
Published:	Case Western Reserve University School of Graduate Studies / OhioLINK 2014
Subjects:	Biology
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=case1396011572

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spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-case13960115722021-08-03T06:23:05Z THE ROLE OF INTEGRIN-SWITCHING AND DEPTOR IN ONCOGENIC TGF-B SIGNALING AND BREAST CANCER METASTASIS Parvani, Jenny G. Biology Breast cancer is a devastating disease that accounts for more than 40,000 deaths per year. Treatment options have vastly improved for patients with localized disease; however, there is currently no cure for patients with metastatic disease. Intuitively, understanding the basic mechanisms of metastasis is critical for the development of appropriate therapeutic interventions. TGF-ß is a pleiotropic cytokine that participates in the development and maintenance of mammary gland homeostasis and structural integrity. Importantly, TGF-ß functions as a powerful tumor suppressor in normal cells, but undergoes a functional metamorphosis to gain tumor-promoting capabilities during cancer progression. These bifurcating effects of TGF-ß function are known as the “TGF-ß paradox” and represent the most confounding aspect of its biology. The gain in oncogenic properties by TGF-ß is likely coupled to its ability to induce Epithelial-Mesenchymal Transition (EMT). EMT is a normal physiological process whereby cuboidal, polarized, and immotile epithelial cells undergo morphological changes that bestows upon them fibroblastoid-like phenotypes that are concomitant with increased invasiveness. Importantly, EMT has been associated with a change in integrin expression profile as well as changes in the mTOR signaling pathway. The findings herein elucidate the roles of ß1¿ß3 integrin switching and Deptor in mediating oncogenic TGF-ß signaling and breast cancer metastasis. Importantly, we demonstrate that inactivation of ß1 integrin induces compensatory upregulation of ß3 integrin that renders sole targeting of ß1 integrin ineffective in the treatment of metastatic breast cancer. Conversely, we show that gene silencing of ß3 integrin by ECO nanoparticle is an effective therapeutic regimen to combat breast cancer metastasis. Lastly, we establish dual roles of Deptor in the regulation of breast cancer metastasis. Collectively, our findings implicate ß3 integrin and Deptor as key players of breast cancer metastasis, with the potential of both being predictive biomarkers. 2014-06-11 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1396011572 http://rave.ohiolink.edu/etdc/view?acc_num=case1396011572 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	Biology
spellingShingle	Biology Parvani, Jenny G. THE ROLE OF INTEGRIN-SWITCHING AND DEPTOR IN ONCOGENIC TGF-B SIGNALING AND BREAST CANCER METASTASIS
author	Parvani, Jenny G.
author_facet	Parvani, Jenny G.
author_sort	Parvani, Jenny G.
title	THE ROLE OF INTEGRIN-SWITCHING AND DEPTOR IN ONCOGENIC TGF-B SIGNALING AND BREAST CANCER METASTASIS
title_short	THE ROLE OF INTEGRIN-SWITCHING AND DEPTOR IN ONCOGENIC TGF-B SIGNALING AND BREAST CANCER METASTASIS
title_full	THE ROLE OF INTEGRIN-SWITCHING AND DEPTOR IN ONCOGENIC TGF-B SIGNALING AND BREAST CANCER METASTASIS
title_fullStr	THE ROLE OF INTEGRIN-SWITCHING AND DEPTOR IN ONCOGENIC TGF-B SIGNALING AND BREAST CANCER METASTASIS
title_full_unstemmed	THE ROLE OF INTEGRIN-SWITCHING AND DEPTOR IN ONCOGENIC TGF-B SIGNALING AND BREAST CANCER METASTASIS
title_sort	role of integrin-switching and deptor in oncogenic tgf-b signaling and breast cancer metastasis
publisher	Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate	2014
url	http://rave.ohiolink.edu/etdc/view?acc_num=case1396011572
work_keys_str_mv	AT parvanijennyg theroleofintegrinswitchinganddeptorinoncogenictgfbsignalingandbreastcancermetastasis AT parvanijennyg roleofintegrinswitchinganddeptorinoncogenictgfbsignalingandbreastcancermetastasis
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THE ROLE OF INTEGRIN-SWITCHING AND DEPTOR IN ONCOGENIC TGF-B SIGNALING AND BREAST CANCER METASTASIS

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