REGULAR ARTICLES

Cell Research (2003); 13(5):343-350

 

TGF-ß1-promoted epithelial-to-mesenchymal transformation and cell adhesion contribute to TGF-ß1-enhanced cell migration in SMMC-7721 cells

 

ZHEN XU1, MIN XIONG SHEN2, DONG ZHU MA1, LI YING WANG1, XI LIANG ZHA1*

1Key Laboratory of Glycoconjugate Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Email: xlzha@shmu.edu.cn
2Medical School, Huzhou Teacher's College, Huzhou Zhejiang 313000, China

*Correspondence: Prof. Xi Liang ZHA, Tel: 0086- 021-54237696

Received May-13-2003 Revised July-28-2003 Accepted-Sept-18-2003

ABSTRACT
Transforming growth factor-ß1 (TGF-ß1), a multi-function polypeptide, is a double-edged sword in cancer. For some tumor cells, TGF-ß1 is a potent growth inhibitor and apoptosis inducer. More commonly, TGF-ß1 loses its growth-inhibitory and apoptosis-inducing effects, but stimulates the metastatic capacity of tumor cells. It is currently little known about TGF-ß1-promoted cell migration in hepatocellular carcinoma (HCC) cells, let alone its mechanism. In this study, we found that TGF-ß1 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-ß1 enhanced the expression of a5ß1 integrin obviously, and subsequently stimulated cell adhesion onto fibronectin (Fn). Furthermore, we observed that TGF-ß1 could also promote SMMC-7721 cells adhesion onto laminin (Ln). Our data also provided evidences that TGF-ß1 induced epithelial-to-mesenchymal transformation (EMT) in SMMC-7721 cells. First, SMMC-7721 cells clearly switched to the spindle shape morphology after TGF-ß1 treatment. Furthermore, TGF-ß1 induced the down-regulation of E-cadherin and the nuclear translocation of ß-catenin. These results indicated that TGF-ß1-promoted cell adhesion and TGF-ß1-induced epithelial-to-mesenchymal transformation might be both responsible for TGF-ß1-enhanced cell migration.
Key words:
TGF-ß1, cell migration, epithelial-to-mesenchymal transformation, a5ß1 integrin.

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