FOCAL ADHESION KINASE (P125(FAK)) EXPRESSION CORRELATES WITH MOTILITY OF HUMAN-MELANOMA CELL-LINES

Focal adhesion kinase (p125(PAK)), a recently characterized protein localized within focal adhesion plaques, is believed to play a role in extracellular matrix-integrin-mediated signal transduction involving cytoskeletal proteins, We studied p125(FAK) expression, distribution, and relation to cell migration in six human melanoma cell. lines. Western blot analysis detected differential expression of p125(FAK) among these lines that was directly proportional to the amount of phosphorylated p125(FAK). Time-lapse image analysis of the cell lines exhibited PO-fold differences in the mean migration rates on fibronectin-coated substrates. Regression analysis revealed that p125(FAK) expression correlated significantly with mean migration rate in the six melanoma lines tested; Double immunofluorescent labeling for p125(FAK) and actin in these lines demonstrated p125(FAK) plaques that were localized to actin stress-fiber termination sites in the periphery of cells. The number of p125(FAK) plaques in the melanoma cell lines was heterogeneous, but the cell lines with more p125(FAK) plaques per cell exhibited significantly higher mean migration rates on fibronectin as compared with cell lines with fewer p125(FAK) plaques per cell. The findings support the hypothesis that focal adhesion tyrosine kinase modulates cytoskeletal function during melanoma cell migration on fibronectin.