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TheScientificWorldJOURNAL
Volume 10 (2010), Pages 1100-1106
http://dx.doi.org/10.1100/tsw.2010.114
Mini-Review Article

The Interaction of Src Kinase with β3 Integrin Tails: A Potential Therapeutic Target in Thrombosis and Cancer

1Dynamics of Cell Adhesion, Hubrecht Institute, University Medical Centre Utrecht, The Netherlands
2Division of Toxicology, Leiden Amsterdam Center for Drug Research, Leiden University, The Netherlands

Received 27 February 2010; Revised 2 May 2010; Accepted 14 May 2010

Academic Editor: Edward J. Benz

Copyright © 2010 Stephan Huveneers and Erik H. J. Danen.

Abstract

Activation of Src family kinases is an important event downstream of integrin adhesion signaling in many cell types. A particularly intriguing connection between an integrin and a Src family kinase was first discovered in platelets, where the selective direct interaction of αIIbβ3 integrins with c-Src promotes full kinase activation of c-Src through its local clustering by the cytoplasmic tail of the β3 integrin subunit. The same integrin β3-c-Src interaction not only drives platelet aggregation, but it also promotes the oncogenic potential of c-Src and drives tumor growth by αvβ3-expressing tumor cells, which may explain why increased activity of c-Src and elevated levels of integrin αvβ3 are often found in the same tumor types. Moreover, recent evidence from patient material and in vivo studies strongly indicate that this oncogenic signaling complex, consisting of c-Src and αvβ3, underlies tumor progression of human tumors. Here, we give an overview of the β3-c-Src interaction and its implications for signaling in platelets and tumor cells, and we mention the possibilities for therapeutic intervention that is aimed at disrupting the β3-c-Src interaction for antithrombotic and anticancer purposes.