The Interaction of Src Kinase with beta 3 Integrin Tails: A Potential Therapeutic Target in Thrombosis and Cancer

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 alpha IIb beta 3 integrins with c-Src promotes full kinase activation of c-Src through its local clustering by the cytoplasmic tail of the beta 3 integrin subunit. The same integrin beta 3-c-Src interaction not only drives platelet aggregation, but it also promotes the oncogenic potential of c-Src and drives tumor growth by av beta 3-expressing tumor cells, which may explain why increased activity of c-Src and elevated levels of integrin alpha v beta 3 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 alpha v beta 3, underlies tumor progression of human tumors. Here, we give an overview of the beta 3-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 beta 3-c-Src interaction for antithrombotic and anticancer purposes