The expression and activity of the c-Src protein tyrosine kinase is frequently increased in carcinomas of breast, colon, and other epithelia and activating mutations in the SRC gene, which delete the C-terminal regulatory Tyr529, have been detected in colon carcinomas. Integrin avb3 is often expressed in such carcinomas and an interaction between wild type c-Src and aIIbb3 has been reported in platelets. In this project we have discovered that oncogenic transformation of epithelial cells by mutationally activated SrcY529F, but not by RasG12V, requires the expression of high levels of integrin avb3 ( PubMed).
Besides oncogenic transformation, activated mutants of Src also cause marked alterations in cellular morphology. These include cell scattering, inhibition of cell-matrix adhesion, loss of cytoskeletal contractility, and assembly of podosomes. These changes are believed to contribute to cancer invasion and metastasis and we have found that they can be uncoupled from oncogenic transformation. We have also found that the different aspects of morphological transformation can be further uncoupled and we have shown that different integrins regulate these processes (manuscript submitted). We are currently testing the cross talk between integrins and Src in vivo.

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