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 pp60c-src and pp62c-yes were measured in the immune complex kinase assay. Relative levels of p125FAK, pp60c-src, and pp62c-yes were determined by immunoblotting.
Results: p125FAK 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 p125FAK was not a significant prognostic factor in survival. A differential activation of pp60c-src and pp62c-yes in colorectal carcinoma liver metastases was observed. However, overexpression of p125FAK was observed in metastases with either pp60c-src or pp62c-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 pp60c-src or pp62c-yes activation in human colorectal carcinoma liver metastases.
Key Words Focal adhesion kinase - Tumor progression - Liver metastasis - Colon cancer
Presented at the 49th Annual Cancer Symposiumof The Society of Surgical Oncology, Atlanta, Georgia, March 21–24, 1996.