title: TGF-beta1-promoted epithelial-to-mesenchymal transformation and cell adhesion contribute to TGF-beta1-enhanced cell migration in SMMC-7721 cells.
abstract: Transforming growth factor-b1 (TGF-beta1), a multi-function polypeptide, is a double-edged sword in cancer. For some tumor cells, TGF-beta1 is a potent growth inhibitor and apoptosis inducer. More commonly, TGF-beta1 loses its growth-inhibitory and apoptosis-inducing effects, but stimulates the metastatic capacity of tumor cells. It is currently little known about TGF-beta1-promoted cell migration in hepatocellular carcinoma (HCC) cells, let alone its mechanism. In this study, we found that TGF-beta1 lost its tumor-suppressive effects, but significantly stimulated cell migration in SMMC-7721 human HCC cells. By FACS and Western blot analysis, we observed that TGF-beta1 enhanced the expression of alpha5beta1 integrin obviously, and subsequently stimulated cell adhesion onto fibronectin (Fn). Furthermore, we observed that TGF-beta1 could also promote SMMC-7721 cells adhesion onto laminin (Ln). Our data also provided evidences that TGF-beta1 induced epithelial-to-mesenchymal transformation (EMT) in SMMC-7721 cells. First, SMMC-7721 cells clearly switched to the spindle shape morphology after TGF-beta1 treatment. Furthermore, TGF-beta1 induced the down-regulation of E-cadherin and the nuclear translocation of beta-catenin. These results indicated that TGF-beta1-promoted cell adhesion and TGF-beta1-induced epithelial-to-mesenchymal transformation might be both responsible for TGF-beta1-enhanced cell migration.
authors.affiliation: Key Laboratory of Glycoconjugate Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xu
authors.forename: Min Xiong
authors.initials: MX
authors.lastname: Shen
authors.forename: Dong Zhu
authors.initials: DZ
authors.lastname: Ma
authors.forename: Li Ying
authors.initials: LY
authors.lastname: Wang
authors.forename: Xi Liang
authors.initials: XL
authors.lastname: Zha
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology*; D015870:Gene Expression; D006801:Humans; D039081:Integrin alpha5beta1 / Q000096:biosynthesis; D007797:Laminin / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1
chemical_list: D039081:Integrin alpha5beta1; D007797:Laminin; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1