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.