The role of c-Src in integrin (α6β4) dependent translational control

BACKGROUND: Integrin α6β4 contributes to cancer progression by stimulating transcription as well as translation of cancer related genes. Our previous study demonstrated that α6β4 stimulates translation initiation of survival factors such as VEGF by activating mTOR pathway. However, the immediate early signaling events that link α6β4 to mTOR activation needs to be defined. RESULTS: In the current studies, we demonstrated that c-Src is an immediate early signaling molecule that acts upstream of α6β4 dependent mTOR activation and subsequent translation of VEGF in MDA-MB-435/β4 and MDA-MB-231 cancer cells. m(7)GTP-Sepharose–binding assay revealed that Src activity is required to form eIF4F complex which is necessary for Cap-dependent translation in α6β4 expressing human cancer cells. CONCLUSIONS: Overall, our studies suggest that integrin β4 and c-Src activation is important early signaling events to lead mTOR activation and cap-dependent translation of VEGF.