mTOR Regulate EMT Through RhoA and Rac1 Pathway in Prostate Cancer
mTOR Regulate EMT Through RhoA and Rac1 Pathway in Prostate Cancer
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mTOR 通过 RhoA 和 Rac1 通路调节前列腺癌的 EMT
DOI：
10.1002/mc.22177
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发表时间：
2015-10-01
影响因子：
4.6
通讯作者：
Liang, ChaoZhao
中科院分区：
文献类型：
--
作者：
Chen, XianGuo;Cheng, HaiYan;Liang, ChaoZhao
近年来，越来越多的研究表明mTOR在肿瘤细胞运动、侵袭和转移的调节中发挥着关键作用。然而，人们对调节前列腺癌上皮间质转化（EMT）的信号机制知之甚少。在本研究中，我们发现前列腺癌组织中Raptor和Rictor的表达水平升高，这可能表明Raptor和Rictor信号通路与前列腺癌的进展和转移相关。通过分别敲除raptor或rictor来抑制mTORC1或mTORC2，前列腺癌的迁移和侵袭被减弱。此外，抑制 Raptor 或 Rictor 后会出现 EMT，其特征是 E-钙粘蛋白、β-连环蛋白、N-钙粘蛋白和波形蛋白等各种标记物的表达水平发生变化。最后，下调 Raptor 和 Rictor 后，细胞迁移和侵袭中至关重要的调节蛋白小 GTPase（RhoA 和 Rac1）失活。这些结果表明 mTOR 至少部分通过下调 RhoA 和 Rac1 信号通路来调节 EMT。我们的研究结果提供了非常有吸引力的新颖靶标策略，即抑制 mTOR 信号通路可能会在早期阶段延缓前列腺癌的迁移和侵袭。 (C) 2014 年 Wiley 期刊公司。
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.