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Interaction of Integrin-Linked Kinase and Miniature Chromosome Maintenance 7–Mediating Integrin α7 Induced Cell Growth Suppression

Authors :
Yan P. Yu
Hui Wang
Yu-Chen Han
Chuanyue Wu
George K. Michalopoulos
Jianhua Luo
Joel Nelson
Source :
Cancer Research. 70:4375-4384
Publication Year :
2010
Publisher :
American Association for Cancer Research (AACR), 2010.

Abstract

Mutation of integrin α7 (ITGA7) was previously identified in multiple human malignancies. Restoration of ITGA7 expression in prostate cancer and leiomyosarcoma cell lines suppressed tumor growth and cell motility both in vitro and in vivo. In this study, we showed that integrin-linked kinase (ILK) binds with miniature chromosome maintenance 7 (MCM7), a DNA replication licensing protein. A 58–amino acid ILK binding motif was identified in the NH2-terminus of MCM7. The expression of ITGA7 induced the phosphorylation of MCM7. Knocking down of ILK abrogated ITGA7-induced MCM7 phosphorylation. ANK, the dominant-negative mutant of ILK, also blocked the phosphorylation of MCM7 induced by ITGA7. The phosphorylation of MCM7 reduced MCM7 chromatin association and inhibited cell growth. A MCM7 mutant that does not bind with ILK did not respond to ITGA7 stimulation, and behaved similarly to a dominant MCM7-negative mutant and neutralized the effect of ITGA7. We conclude that ILK interaction with MCM7 and MCM7 phosphorylation may be a critical event in ITGA7 signaling pathway, leading to tumor suppression. Cancer Res; 70(11); 4375–84. ©2010 AACR.

Details

ISSN :
15387445 and 00085472
Volume :
70
Database :
OpenAIRE
Journal :
Cancer Research
Accession number :
edsair.doi...........e7d145ba8bbc56f8bfa320e0684f51ab
Full Text :
https://doi.org/10.1158/0008-5472.can-09-4403