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Down-regulation of CMTM8 induces epithelial-to-mesenchymal transition-like changes via c-MET/extracellular signal-regulated kinase (ERK) signaling
Zhang W.2; Mendoza M.C.3; Pei X.2; Ilter D.3; Mahoney S.J.3; Zhang Y.2; Ma D.2; Blenis J.3; Wang Y.2
2012-04-06
Source PublicationJournal of Biological Chemistry
ISSN00219258 1083351X
Volume287Issue:15Pages:11850-11858
AbstractThe acquisition of an invasive phenotype is a critical turning point for malignant tumor cells. CMTM8, a potential tumor suppressor, is frequently down-regulated in solid tumors, and its overexpression induces tumor cell apoptosis. Here, we identify a new role for CMTM8 in regulating tumor cell migration. Reducing CMTM8 expression in HepG2 hepatocellular carcinoma cells results in the acquisition of epithelial-to-mesenchymal transition (EMT) features, including a morphological change from organized epithelial sheets to scattered fibroblastlike shapes, reduction of the epithelial marker E-cadherin, and an increased invasive and migratory ability. These phenotypic changes are mediated in large part by the ERK-MAPK pathway, as the MEK inhibitor U0126 and shRNA-mediated knockdown of ERK2 significantly reversed these phenotypes. Hepatocyte growth factor binding to the c-MET receptor is known to induce EMT in HepG2 cells. We found that CMTM8 knockdown in HepG2 cells induced c-MET signaling and ERK activation. Inhibition of c-MET signaling with the small molecule inhibitor SU11274 or c-MET RNAi blocked the EMT-like changes following CMTM8 knockdown. CMTM8 overexpression in HepG2 cells inhibited hepatocyte growth factor-induced EMT-like morphological changes and cell motility. Down-regulation of CMTM8 also promoted an EMT-like change in MCF-10A cells, indicating a broader role for CMTM8 in regulating cellular transformation. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI10.1074/jbc.M111.258236
URLView the original
Language英語
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Cited Times [WOS]:35   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Beijing Shijitan General Hospital
2.Peking University Health Science Center
3.Harvard Medical School
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GB/T 7714
Zhang W.,Mendoza M.C.,Pei X.,et al. Down-regulation of CMTM8 induces epithelial-to-mesenchymal transition-like changes via c-MET/extracellular signal-regulated kinase (ERK) signaling[J]. Journal of Biological Chemistry,2012,287(15):11850-11858.
APA Zhang W..,Mendoza M.C..,Pei X..,Ilter D..,Mahoney S.J..,...&Wang Y..(2012).Down-regulation of CMTM8 induces epithelial-to-mesenchymal transition-like changes via c-MET/extracellular signal-regulated kinase (ERK) signaling.Journal of Biological Chemistry,287(15),11850-11858.
MLA Zhang W.,et al."Down-regulation of CMTM8 induces epithelial-to-mesenchymal transition-like changes via c-MET/extracellular signal-regulated kinase (ERK) signaling".Journal of Biological Chemistry 287.15(2012):11850-11858.
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