Overexpression of focal adhesion kinase (p125FAK) in human colorectal carcinoma liver metastases: independence from c-src or c-yes activation.
BACKGROUND
p125FAK, pp60C-src, and pp62c-yes are protein tyrosine kinases that function in signaling pathways regulating cell adhesion, migration, and growth. The expression and tyrosine kinase activities of pp60c-src and pp62c-yes, and the expression of p125FAK are increased in colorectal tumor metastases relative to normal mucosa. This study investigates whether differences in the activation of pp60c-src and pp62c-yes in colorectal liver metastases correlated with differences in p125FAK expression and whether prognostic significance could be demonstrated from the extent of expression of p125FAK 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.
Han
N M
NM
Department of Surgery, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Fleming
R Y
RY
Curley
S A
SA
Gallick
G E
GE
D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000473:pathology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000556:secondary*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D019061:src-Family Kinases / Q000378:metabolism*
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D019061:src-Family Kinases