Abstract.
Physical forces can activate colon cancer cell adhesion, critical for metastasis. Paxillin is phosphorylated by FAK and required for pressure-stimulated adhesion. However, whether paxillin acts as an inert scaffolding protein or whether paxillin phosphorylation is required is unknown. Transfection with paxillin point-phosphorylation mutants demonstrated that phosphorylation at tyrosines 31 and 118 together is necessary for pressure-stimulated adhesion. We further evaluated potential paxillin partners. Reducing the adaptor protein Crk or the focal adhesion protein p130Cas blocked pressure-stimulated adhesion. Furthermore, Crk and p130Cas both displayed increased co-immunoprecipitation with paxillin in response to increased pressure, except in cells transfected with a Y31Y118 paxillin mutant. Inhibiting the small GTPase Rac1 also abolished pressure-stimulated adhesion, and reducing paxillin by siRNA blocked Rac1 phosphorylation by pressure. Thus, paxillin phosphorylation at tyrosines 31 and 118 together is necessary for pressure-induced adhesion. Paxillin, Crk and Cas form a trimeric complex that activates Rac1 and mediates this effect.
Similar content being viewed by others
Author information
Authors and Affiliations
Corresponding author
Additional information
Received 21 January 2008; received after revision 4 March 2008; accepted 19 March 2008
Rights and permissions
About this article
Cite this article
Downey, C., Craig, D.H. & Basson, M.D. Pressure activates colon cancer cell adhesion via paxillin phosphorylation, Crk, Cas, and Rac1. Cell. Mol. Life Sci. 65, 1446–1457 (2008). https://doi.org/10.1007/s00018-008-8038-x
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00018-008-8038-x