Overexpression of focal adhesion kinase (p125(FAK)) in human colorectal carcinoma liver metastases: Independence from c-src or c-yes activation

Background: p125(FAK), pp60(c-src), and pp62(c-yes) are protein tyrosine kinases that function in signaling pathways regulating cell adhesion, migration, and growth. The expression and tyrosine kinase activities of pp60(c-src) and pp62(c-yes), and the expression of p125(FAK) are increased in colorectal tumor metastases relative to normal mucosa. This study investigates whether differences in the activation of pp60(c-src) and pp62(c-yes) in colorectal liver metastases correlated with differences in p125(FAK) expression and whether prognostic significance could be demonstrated from the extent of expression of p125(FAK) in metastases. Methods: Activities of pp60(c-src) and pp62(c-yes) were measured in the immune complex kinase assay. Relative levels of p125(FAK), pp60(c-src), and pp62(c-yes) were determined by immunoblotting. Results: p125(FAK) was overexpressed in 29 of 30 colorectal cancer liver metastases (range of two- to 195-fold increase compared with normal mucosa). The degree of overexpression of p125(FAK) was not a significant prognostic factor in survival. A differential activation of pp60(c-src) and pp62(c-yes) in colorectal carcinoma liver metastases was observed. However, overexpression of p125(FAK) was observed in metastases with either pp60(c-src) or pp62(c-yes) activated in colorectal carcinoma liver metastases. Conclusions: p125FAK overexpression appears to be a marker present in colorectal cancer cells with a metastatic phenotype. Furthermore, p125FAK overexpression is independent of pp60(c-sc) or pp62(c-yes) activation in human colorectal carcinoma liver metastases.