3 years ago

The role of small GTPases of the Rho/Rac family in TGF-β-induced EMT and cell motility in cancer

Hendrik Lehnert, David Witte, Hendrik Ungefroren
Background: This article focuses on the role of Rho family GTPases, particularly Rac1 and Rac1b in TGF-β-induced epithelial-mesenchymal transition (EMT) and EMT-associated responses such as cell migration, invasion, and metastasis in cancer. Results: EMT is considered a prerequisite for cells to adopt a motile and invasive phenotype and eventually become metastatic. A major regulator of EMT and metastasis in cancer is TGF-β, and its specific functions on tumor cells are mediated beside Smad proteins and mitogen-activated protein kinases (MAPKs) by small GTPases of the Rho/Rac1 family. Available data point to extensive signaling crosstalk between TGF-β and various Rho GTPases, and in particular a synergistic role of Rho and Rac1 during EMT and cell motility in normal and neoplastic epithelial cells. In contrast, the Rac1-related isoform, Rac1b, emerges as an endogenous inhibitor of Rac1 in TGF-β signaling, at least in pancreatic carcinoma cells. Conclusions: Given the tumor-promoting role of TGF-β in late-stage carcinomas and the intimate crosstalk of Rho/Rac1/Rac1b and TGF-β signaling in various tumor cell responses, targeting specific Rho GTPases may allow for selective interference with prooncogenic TGF-β responses to aid in anticancer treatments. Developmental Dynamics, 2017. © 2017 Wiley Periodicals, Inc.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/dvdy.24505

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