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Originally published In Press as doi:10.1074/jbc.M611680200 on May 18, 2007

J. Biol. Chem., Vol. 282, Issue 28, 20455-20466, July 13, 2007
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The MIG-2/Integrin Interaction Strengthens Cell-Matrix Adhesion and Modulates Cell Motility*

Xiaohua Shi{ddagger}, Yan-Qing Ma§1, Yizeng Tu{ddagger}, Ka Chen{ddagger}, Shan Wu{ddagger}, Koichi Fukuda§, Jun Qin§, Edward F. Plow§, and Chuanyue Wu{ddagger}2

From the {ddagger}Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261 and the §Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195

Integrin-mediated cell-matrix adhesion plays an important role in control of cell behavior. We report here that MIG-2, a widely expressed focal adhesion protein, interacts with beta1 and beta3 integrin cytoplasmic domains. Integrin binding is mediated by a single site within the MIG-2 FERM domain. Functionally, the MIG-2/integrin interaction recruits MIG-2 to focal adhesions. Furthermore, using {alpha}IIbbeta3 integrin-expressing Chinese hamster ovary cells, a well described model system for integrin activation, we show that MIG-2 promotes integrin activation and enhances cell-extracellular matrix adhesion. Although MIG-2 is expressed in many cell types, it is deficient in certain colon cancer cells. Expression of MIG-2, but not of an integrin binding-defective MIG-2 mutant, in MIG-2-null colon cancer cells strengthened cell-matrix adhesion, promoted focal adhesion formation, and reduced cell motility. These results suggest that the MIG-2/integrin interaction is an important element in the cellular control of integrin-mediated cell-matrix adhesion and that loss of this interaction likely contributes to high motility of colon cancer cells.

Received for publication, December 20, 2006 , and in revised form, April 20, 2007.

* This work was supported in part by National Institutes of Health Grants GM65188 and DK54639 (to C. W.), Grant HL58758 (to J. Q.), and Grant HL073311 (to E. F. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Supported by a fellowship from the American Heart Association, Ohio Valley Affiliate.

2 To whom correspondence should be addressed: Dept. of Pathology, University of Pittsburgh, 707B Scaife Hall, 3550 Terrace St., Pittsburgh, PA 15261. Tel.: 412-648-2350; Fax: 509-561-4062; E-mail: carywu{at}pitt.edu.


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