The interaction of SRC kinase with beta3 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 alphaIIbbeta3 integrins with c-Src promotes full kinase activation of c-Src through its local clustering by the cytoplasmic tail of the beta3 integrin subunit. The same integrin beta3-c-Src interaction not only drives platelet aggregation, but it also promotes the oncogenic potential of c-Src and drives tumor growth by alphavbeta3-expressing tumor cells, which may explain why increased activity of c-Src and elevated levels of integrin alphavbeta3 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 alphavbeta3, underlies tumor progression of human tumors. Here, we give an overview of the beta3-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 beta3-c-Src interaction for antithrombotic and anticancer purposes.
Huveneers
Stephan
S
Dynamics of Cell Adhesion, Hubrecht Institute and University Medical Centre Utrecht, The Netherlands. s.huveneers@hubrecht.eu
Danen
Erik H J
EH
D002455:Cell Division; D018450:Disease Progression; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D011485:Protein Binding; D013927:Thrombosis / Q000188:drug therapy / Q000201:enzymology*; D019061:src-Family Kinases / Q000378:metabolism*
D039661:Integrin beta3; D040201:Platelet Membrane Glycoprotein IIb; D019061:src-Family Kinases