Requirement for focal adhesion kinase in tumor cell adhesion

Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase and a major phosphotyrosine-containing protein. FAK is found in cell-matrix attac hment sites (focal adhesions), and is activated on integrin-ligand binding and by other signaling pathways. Several roles have been proposed for FAK; here we report a novel function. We observed abundant FAK protein in all hu man melanoma cell lines tested except COLO839, a line that grows predominan tly in suspension and was derived from peripheral blood. Five adherent line s, isolated from solid metastases in the same patient as COLO839, did expre ss FAK. We derived four adherent sublines from COLO839. These did express F AK, even when plated on bacteriological plastic, to which they did not adhe re. Thus, substrate attachment was not required for FAK expression. Three o f the adherent sublines were then grown in the presence of antisense oligon ucleotides to the initial FAK coding sequence. All showed substantially red uced FAK expression and, interestingly, the cells largely detached from the substrate while continuing to grow. Similar results were obtained with an independent melanoma line, DX3. Thus, FAK expression appears to be required by melanoma cells for substrate adhesion.