title: TMEPAI regulates EMT in lung cancer cells by modulating the ROS and IRS-1 signaling pathways.
abstract: The epithelial-mesenchymal transition (EMT) has been implicated in various pathophysiological processes, including cancer cell migration and distal metastasis. Reactive oxygen species (ROS) and insulin receptor substrate-1 (IRS-1) are important in cancer progression and regulation of EMT. To explore the biological significance and regulatory mechanism of EMT, we determined the expression, the biological function and the signaling pathway of prostate transmembrane protein, androgen induced-1 (TMEPAI), during the induction of EMT and cell migration. Transforming growth factor (TGF)-β1 significantly upregulated the expression of TMEPAI during EMT in human lung adenocarcinoma. Depletion of TMEPAI abolished TGF-β1-induced downregulation of ferritin heavy chain and the subsequent generation of ROS, thus suppressing TGF-β1-induced EMT and cell migration. In addition, increased ROS production and overexpression of TMEPAI downregulated the level of IRS-1. Both the addition of H2O2 and IRS-1 small interfering RNA rescued the ability of TGF-β1 to induce EMT in TMEPAI-depleted cells. Remarkably, the levels of TMEPAI in lung tumor tissues are very high, whereas its expression in normal lung epithelium is very low. Moreover, TMEPAI expression was positively correlated with the cell mesenchymal phenotype and migration potential. Our work reveals that TMEPAI contributes to TGF-β1-induced EMT through ROS production and IRS-1 downregulation in lung cancer cells.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Kai
authors.initials: K
authors.lastname: He
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.forename: Xinwang
authors.initials: X
authors.lastname: Yuan
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Hongbin
authors.initials: H
authors.lastname: Ji
authors.forename: Jianguo
authors.initials: J
authors.lastname: Song
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D001052:Apoferritins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D008565:Membrane Proteins; C412868:PMEPA1 protein, human; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D001052:Apoferritins; D006861:Hydrogen Peroxide