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Journal of Mammary Gland Biology and Neoplasia

Published in:

01-06-2010

The Pathophysiology of Epithelial-Mesenchymal Transition Induced by Transforming Growth Factor-β in Normal and Malignant Mammary Epithelial Cells

Authors: Molly A. Taylor, Jenny G. Parvani, William P. Schiemann

Published in: Journal of Mammary Gland Biology and Neoplasia | Issue 2/2010

Abstract

Epithelial-mesenchymal transition (EMT) is an essential process that drives polarized, immotile mammary epithelial cells (MECs) to acquire apolar, highly migratory fibroblastoid-like features. EMT is an indispensable process that is associated with normal tissue development and organogenesis, as well as with tissue remodeling and wound healing. In stark contrast, inappropriate reactivation of EMT readily contributes to the development of a variety of human pathologies, particularly those associated with tissue fibrosis and cancer cell invasion and metastasis, including that by breast cancer cells. Although metastasis is unequivocally the most lethal aspect of breast cancer and the most prominent feature associated with disease recurrence, the molecular mechanisms whereby EMT mediates the initiation and resolution of breast cancer metastasis remains poorly understood. Transforming growth factor-β (TGF-β) is a multifunctional cytokine that is intimately involved in regulating numerous physiological processes, including cellular differentiation, homeostasis, and EMT. In addition, TGF-β also functions as a powerful tumor suppressor in MECs, whose neoplastic development ultimately converts TGF-β into an oncogenic cytokine in aggressive late-stage mammary tumors. Recent findings have implicated the process of EMT in mediating the functional conversion of TGF-β during breast cancer progression, suggesting that the chemotherapeutic targeting of EMT induced by TGF-β may offer new inroads in ameliorating metastatic disease in breast cancer patients. Here we review the molecular, cellular, and microenvironmental factors that contribute to the pathophysiological activities of TGF-β during its regulation of EMT in normal and malignant MECs.

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Title: The Pathophysiology of Epithelial-Mesenchymal Transition Induced by Transforming Growth Factor-β in Normal and Malignant Mammary Epithelial Cells
Authors: Molly A. Taylor
Jenny G. Parvani
William P. Schiemann
Publication date: 01-06-2010
Publisher: Springer US
Published in: Journal of Mammary Gland Biology and Neoplasia / Issue 2/2010
Print ISSN: 1083-3021
Electronic ISSN: 1573-7039
DOI: https://doi.org/10.1007/s10911-010-9181-1

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Epithelial-Mesenchymal Transition (EMT) in Tumor-Initiating Cells and Its Clinical Implications in Breast Cancer

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