title: Tensin4 is up-regulated by EGF-induced ERK1/2 activity and promotes cell proliferation and migration in hepatocellular carcinoma.
abstract: The focal adhesion protein Tensin4, also known as cten (c-terminal tensin like), is structurally distinct from the three other members in the Tensin family. Its expression and potential functions in cancers including hepatocellular carcinoma (HCC) are not well understood. With immunohistochemistry, 43% (13/30) of our human HCC cases showed up-regulation of Tensin4 as compared with their corresponding non-tumorous livers. In HCC cells, treatment with epidermal growth factor (EGF) significantly induced Tensin4 transcript and protein expression, while treatment with pharmacological inhibitors against the MEK1/2 kinases abolished such induction, suggesting that Tensin4 expression was dependent on Ras/MAPK signaling. With immunofluorescence microscopy, the focal adhesion localization of Tensin4 was confirmed in HCC cells. Significantly, detailed examination using a panel of Tensin4 deletion constructs revealed that this specific focal adhesion localization required the N-terminal region together with the C-terminal SH2 domain. Up-regulation of ERK signaling by EGF in the HCC cells resulted in a change to a mesenchymal cell-like morphology through modulation of the actin cytoskeleton. Functionally, stable Tensin4 knockdown in SMMC-7721 HCC cells resulted in reduced cell proliferation and migration in vitro. Taken together, our data suggest that Tensin4 may play a pro-oncogenic role in HCC, possibly functioning as a downstream effector of Ras/MAPK signaling.
authors.affiliation: Department of Pathology and State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong.
authors.forename: Lo-Kong
authors.initials: LK
authors.lastname: Chan
authors.affiliation: Department of Pathology and State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong.
authors.forename: Yung-Tuen
authors.initials: YT
authors.lastname: Chiu
authors.affiliation: Department of Pathology and State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong.
authors.forename: Karen Man-Fong
authors.initials: KM
authors.lastname: Sze
authors.affiliation: Department of Pathology and State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong.
authors.forename: Irene Oi-Lin
authors.initials: IO
authors.lastname: Ng
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D022001:Focal Adhesions; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008840:Microfilament Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D015398:Signal Transduction; D000070876:Tensins; D015854:Up-Regulation; D018909:src Homology Domains
chemical_list: D008840:Microfilament Proteins; C000603371:TNS4 protein, human; D000070876:Tensins; D004815:Epidermal Growth Factor
keywords: EGF; ERK1/2 activity; HCC; cten