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

  • Molly A. Taylor
  • Jenny G. Parvani
  • William P. SchiemannEmail author


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.


Epithelial-mesenchymal Transition Metastasis Signal transduction Transforming growth factor-β Tumor microenvironment 



α-smooth muscle actin


Bone morphogenic protein


Extracellular matrix


Epidermal growth factor


Epithelial-mesenchymal transition


Extracellular signal-regulated kinase


Focal adhesion kinase


c-Jun N-terminal kinase

MAP kinase

Mitogen-activated protein kinase


Mammary epithelial cell


Mammalian target of rapamycin


Mesenchymal-epithelial transition


Metastasis associated protein 3


Nuclear factor-κB


Plasminogen activator inhibitor


Platelet-derived growth factor




TGF-β type I receptor


TGF-β type II receptor


TGF-β type III receptor


Transforming growth factor-β


Urokinase plasminogen activator


uPA receptor


Zonula occluden-1



We thank members of the Schiemann Laboratory for critical comments and reading of the manuscript. W.P.S. was supported by grants from the National Institutes of Health (CA114039 and CA129359), the Komen Foundation (BCTR0706967), and the Department of Defense (BC084651), while M.A.T. was supported by the Department of Defense (BC093128).


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Molly A. Taylor
    • 1
  • Jenny G. Parvani
    • 1
  • William P. Schiemann
    • 1
    Email author
  1. 1.Case Comprehensive Cancer CenterCase Western Reserve UniversityClevelandUSA

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