The pathophysiology of epithelial-mesenchymal transition induced by transforming growth factor-beta in normal and malignant mammary epithelial cells.
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-beta (TGF-beta) is a multifunctional cytokine that is intimately involved in regulating numerous physiological processes, including cellular differentiation, homeostasis, and EMT. In addition, TGF-beta also functions as a powerful tumor suppressor in MECs, whose neoplastic development ultimately converts TGF-beta 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-beta during breast cancer progression, suggesting that the chemotherapeutic targeting of EMT induced by TGF-beta 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-beta during its regulation of EMT in normal and malignant MECs.
Taylor
Molly A
MA
Case Comprehensive Cancer Center, Case Western Reserve University, Wolstein Research Building, 2103 Cornell Road, Cleveland, OH 44106, USA.
Parvani
Jenny G
JG
Schiemann
William P
WP
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D054337:Cell Dedifferentiation; D002454:Cell Differentiation; D054338:Cell Transdifferentiation; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000503:physiopathology; D042361:Mammary Glands, Human / Q000378:metabolism / Q000503:physiopathology*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009362:Neoplasm Metastasis; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology*
D016212:Transforming Growth Factor beta
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