mTOR Regulate EMT Through RhoA and Rac1 Pathway in Prostate Cancer

Recently, an increasing number of studies have suggested that mTOR plays a critical role in the regulation of tumor cell motility, invasion and cancer metastasis. However, little is known about the signaling mechanisms in regulating epithelial-mesenchymal transition (EMT) of prostate cancer. In this study, we found that the expression levels of Raptor and Rictor in prostate cancer tissues were elevated, which may suggest that Raptor and Rictor signaling pathways are associated with prostate cancer progression and metastasis. Inhibition of mTORC1 or mTORC2 by knock down of raptor or rictor, respectively, migration and invasion of prostate cancer were attenuated. Furthermore, EMT, a characterized by the changed expression levels of various markers like E-cadherin, beta-catenin, N-cadherin, and vimentin emergend following inhibition of Raptor or Rictor. Finally, the small GTPases (RhoA and Rac1) which were crucial regulatory proteins in cell migration and invasion were inactivited after downregulating Raptor and Rictor. These results suggest that mTOR regulate EMT at least in part by down regulation of RhoA and Rac1 signaling pathways. Our findings provide novel very attractive target strategies that the inhibition of mTOR signaling pathways may retard prostate cancer migration and invasion at early stages. (C) 2014 Wiley Periodicals, Inc.