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J. Biol. Chem., Vol. 282, Issue 3, 1830-1837, January 19, 2007

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JAM-C Regulates Tight Junctions and Integrin-mediated Cell Adhesion and Migration^*

Guillaume Mandicourt, Sandra Iden, Klaus Ebnet, Michel Aurrand-Lions, and Beat A. Imhof¹

From the Department of Pathology and Immunology, the University Medical Center, CH 1211 Geneva 4, Switzerland and the Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Munster, D-48149 Münster, Germany

Junctional Adhesion Molecules (JAMs) have been described as major components of tight junctions in endothelial and epithelial cells. Tight junctions are crucial for the establishment and maintenance of cell polarity. During tumor development, they are remodeled, enabling neoplastic cells to escape from constraints imposed by intercellular junctions and to adopt a migratory behavior. Using a carcinoma cell line we tested whether JAM-C could affect tight junctions and migratory properties of tumor cells. We show that transfection of JAM-C improves the tight junctional barrier in tumor cells devoid of JAM-C expression. This is dependent on serine 281 in the cytoplasmic tail of JAM-C because serine mutation into alanine abolishes the specific localization of JAM-C in tight junctions and establishment of cell polarity. More importantly, the same mutation stimulates integrin-mediated cell migration and adhesion via the modulation of 1 and 3 integrin activation. These results highlight an unexpected function for JAM-C in controlling epithelial cell conversion from a static, polarized state to a pro-migratory phenotype.

Received for publication, June 13, 2006 , and in revised form, September 29, 2006.

^* This work was supported by Le Fonds National Suisse Grants 3100AO-100697/1 (to B. A. I.) and 310000-112551/1 (to M. A. L.), La Ligue Contre Le Cancer Grant OCS-01653-02-2005, and Deutsche Forschungsgemeinschaft Grant EB16012-3, SPP1111^* (to K. E.). 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S4.

¹ To whom correspondence should be addressed: Dept. of Pathology and Immunology, University Medical Center, 1 Rue Michel-Servet, CH 1211 Geneva 4, Switzerland. Tel.: 41-22-379-57-47; Fax: 41-22-379-57-46; E-mail: beat.imhof{at}medecine.unige.ch.

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