Focal adhesion kinase (p125FAK) expression correlates with motility of human melanoma cell lines.
Focal adhesion kinase (p125FAK), 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 p125FAK expression, distribution, and relation to cell migration in six human melanoma cell lines. Western blot analysis detected differential expression of p125FAK among these lines that was directly proportional to the amount of phosphorylated p125FAK. Time-lapse image analysis of the cell lines exhibited 10-fold differences in the mean migration rates on fibronectin-coated substrates. Regression analysis revealed that p125FAK expression correlated significantly with mean migration rate in the six melanoma lines tested. Double immunofluorescent labeling for p125FAK and actin in these lines demonstrated p125FAK plaques that were localized to actin stress-fiber termination sites in the periphery of cells. The number of p125FAK plaques in the melanoma cell lines was heterogeneous, but the cell lines with more p125FAK plaques per cell exhibited significantly higher mean migration rates on fibronectin as compared with cell lines with fewer p125FAK plaques per cell. The findings support the hypothesis that focal adhesion tyrosine kinase modulates cytoskeletal function during melanoma cell migration on fibronectin.
Akasaka
T
T
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
van Leeuwen
R L
RL
Yoshinaga
I G
IG
Mihm
M C
MC
Byers
H R
HR
D015815:Cell Adhesion Molecules / Q000032:analysis*; D002465:Cell Movement; D005455:Fluorescent Antibody Technique; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human