Increased integrin alpha5beta1 heterodimer formation and reduced c-Jun expression are involved in integrin beta1 overexpression-mediated cell growth arrest.
Integrins, heterodimers of alpha and beta subunits, are a family of cell surface molecules mediating cell-cell and cell-extracellular matrix interaction. The largest subgroup is formed by the beta(1) subunit containing integrins which consist of 12 members with different ligand-binding properties. We previously reported that overexpressed integrin beta(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 beta(1) subunit overexpression in different cancer cell lines. The upregulated CDK inhibitors induced by beta(1) integrin overexpression were essential for this integrin-mediated growth arrest. Reduced c-Jun level after integrin beta(1) overexpression plays an important role in the transcriptional activation of p21 through the Sp1 sites. Solely overexpressed beta(1) subunit could induce the expression of diverse alpha subunit in different cell lines, among which alpha(5) subunit was found to be correlated with integrin beta(1)-mediated growth arrest. Relative lack of ECM-integrin interaction might be a reason for integrin beta(1) overexpression-mediated growth arrest. These results helped us understand more about the mechanisms that integrins regulate cell growth.
Fang
Zhengyu
Z
Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, PR China.
Yao
Wantong
W
Fu
Yi
Y
Wang
Li-Ying
LY
Li
Zengxia
Z
Yang
Yong
Y
Shi
Yinghong
Y
Qiu
Shuangjian
S
Fan
Jia
J
Zha
Xiliang
X
D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D039482:Integrin alpha5 / Q000235:genetics* / Q000378:metabolism; D039081:Integrin alpha5beta1 / Q000096:biosynthesis / Q000235:genetics*; D019012:Integrin beta1 / Q000235:genetics* / Q000378:metabolism; D055503:Protein Multimerization; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics*; D015533:Transcriptional Activation; D015854:Up-Regulation
D050759:Cyclin-Dependent Kinase Inhibitor p21; D039482:Integrin alpha5; D039081:Integrin alpha5beta1; D019012:Integrin beta1; D016755:Proto-Oncogene Proteins c-jun; D016329:Sp1 Transcription Factor; D050760:Cyclin-Dependent Kinase Inhibitor p27