Migration is a complex process that, besides its various physiological functions in embryogenesis and adult tissues, plays a crucial role in cancer cell invasion and metastasis. The focus of this study is the involvement and collaboration of Akt, focal adhesion kinase (FAK), and Src kinases in migration and invasiveness of colorectal cancer cells. We show that all three kinases can be found in one protein complex; nevertheless, the interaction between Akt and Src is indirect and mediated by FAK. Interestingly, induced Akt signaling causes an increase in tyrosine phosphorylation of FAK, but this increase is attenuated by the Src inhibitor SU6656. We also show that active Akt strongly stimulates cell migration, but this phenomenon is fully blocked by FAK knockdown or partly by inhibition of Src kinase. In addition, we found that all three kinases were indispensable for the successful invasion of colorectal cancer cells. Altogether, the presented data bring new insights into the mechanism how the phosphatidylinositol-3-kinase (PI3-K)/Akt pathway can influence migration of colorectal adenocarcinoma cells. Because FAK is indispensable for cell movements and functions downstream of Akt, our results imply FAK kinase as a potential key molecule during progression of tumors with active PI3-K/Akt signaling.

Institute of Molecular Genetics Academy of Sciences of the Czech Republic Prague Czech Republic

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