title: mTOR regulate EMT through RhoA and Rac1 pathway in prostate cancer.
abstract: 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, β-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.
authors.affiliation: Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: XianGuo
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, PR China.|Anhui Provincial Laboratory of Microbiology & Parasitology, Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: HaiYan
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: TengFei
authors.initials: T
authors.lastname: Pan
authors.affiliation: Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Microbiology and Parasitology, Anhui Medical University, Hefei, Anhui, PR China.|Anhui Provincial Laboratory of Microbiology & Parasitology, Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: CuiPing
authors.initials: C
authors.lastname: Ren
authors.affiliation: Anhui Provincial Laboratory of Microbiology & Parasitology, Anhui Medical University, Hefei, Anhui, PR China.|Comprehensive Laboratory of Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: DaKe
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Biochemistry, Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: XiaoJun
authors.initials: X
authors.lastname: Zha
authors.affiliation: Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: ChaoZhao
authors.initials: C
authors.lastname: Liang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics* / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076223:Regulatory-Associated Protein of mTOR; D015398:Signal Transduction / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*; D014746:Vimentin / Q000235:genetics; D051176:beta Catenin / Q000235:genetics; D020830:rac1 GTP-Binding Protein / Q000235:genetics*; D020742:rhoA GTP-Binding Protein / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D015820:Cadherins; D002352:Carrier Proteins; C107953:RAC1 protein, human; C492571:RICTOR protein, human; C463659:RPTOR protein, human; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076223:Regulatory-Associated Protein of mTOR; D014746:Vimentin; D051176:beta Catenin; C066737:RHOA protein, human; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein
keywords: EMT; mTOR; prostate cancer