TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis

作者：Hao Yang, D.A. Baker, Peter ten Dijke · 发表于：International Journal of Molecular Sciences · 年份：2019 · DOI：10.3390/ijms20112767 · 被引用次数：1178 · 研究领域：Cancer-related molecular mechanisms research、MicroRNA in disease regulation、TGF-β signaling in diseases

Transforming growth factor β (TGF-β) is a secreted cytokine that regulates cell proliferation, migration, and the differentiation of a plethora of different cell types. Consistent with these findings, TGF-β plays a key role in controlling embryogenic development, inflammation, and tissue repair, as well as in maintaining adult tissue homeostasis. TGF-β elicits a broad range of context-dependent cellular responses, and consequently, alterations in TGF-β signaling have been implicated in many diseases, including cancer. During the early stages of tumorigenesis, TGF-β acts as a tumor suppressor by inducing cytostasis and the apoptosis of normal and premalignant cells. However, at later stages, when cancer cells have acquired oncogenic mutations and/or have lost tumor suppressor gene function, cells are resistant to TGF-β-induced growth arrest, and TGF-β functions as a tumor promotor by stimulating tumor cells to undergo the so-called epithelial-mesenchymal transition (EMT). The latter leads to metastasis and chemotherapy resistance. TGF-β further supports cancer growth and progression by activating tumor angiogenesis and cancer-associated fibroblasts and enabling the tumor to evade inhibitory immune responses. In this review, we will consider the role of TGF-β signaling in cell cycle arrest, apoptosis, EMT and cancer cell metastasis. In particular, we will highlight recent insights into the multistep and dynamically controlled process of TGF-β-induced EMT and the functions of mi...