Increased integrin α5β1 heterodimer formation and reduced c-Jun expression are involved in integrin β1 overexpression-mediated cell growth arrest

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 β1 subunit containing integrins which consist of 12 members with different ligand‐binding properties. We previously reported that overexpressed integrin β1 subunit in the hepatocellular carcinoma cell line SMMC‐7721 imposed a growth inhibitory effect through the upregulation of p21cip1 and p27kip1. In this study, we confirmed the growth inhibitory effect of β1 subunit overexpression in different cancer cell lines. The upregulated CDK inhibitors induced by β1 integrin overexpression were essential for this integrin‐mediated growth arrest. Reduced c‐Jun level after integrin β1 overexpression plays an important role in the transcriptional activation of p21 through the Sp1 sites. Solely overexpressed β1 subunit could induce the expression of diverse α subunit in different cell lines, among which α5 subunit was found to be correlated with integrin β1‐mediated growth arrest. Relative lack of ECM–integrin interaction might be a reason for integrin β1 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.