Increased integrin α5β1 heterodimer formation and reduced c-Jun expression are involved in integrin β1 overexpression-mediated cell growth arrest
✍ Scribed by Zhengyu Fang; Wantong Yao; Yi Fu; Li-Ying Wang; Zengxia Li; Yong Yang; Yinghong Shi; Shuangjian Qiu; Jia Fan; Xiliang Zha
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 557 KB
- Volume
- 109
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
Integrins, heterodimers of α and β subunits, are a family of cell surface molecules mediating cell–cell and cell–extracellular matrix interaction. The largest subgroup is formed by the β~1~ subunit containing integrins which consist of 12 members with different ligand‐binding properties. We previously reported that overexpressed integrin β~1~ subunit in the hepatocellular carcinoma cell line SMMC‐7721 imposed a growth inhibitory effect through the upregulation of p21^cip1^ and p27^kip1^. In this study, we confirmed the growth inhibitory effect of β~1~ subunit overexpression in different cancer cell lines. The upregulated CDK inhibitors induced by β~1~ integrin overexpression were essential for this integrin‐mediated growth arrest. Reduced c‐Jun level after integrin β~1~ overexpression plays an important role in the transcriptional activation of p21 through the Sp1 sites. Solely overexpressed β~1~ subunit could induce the expression of diverse α subunit in different cell lines, among which α~5~ subunit was found to be correlated with integrin β~1~‐mediated growth arrest. Relative lack of ECM–integrin interaction might be a reason for integrin β~1~ overexpression‐mediated growth arrest. These results helped us understand more about the mechanisms that integrins regulate cell growth. J. Cell. Biochem. 109: 383–395, 2010. © 2009 Wiley‐Liss, Inc.