EFFECT OF EGF ON CELL-MATRIX INTERACTION AND TYROSINE PHOSPHORYLATION OF THE p125 FOCAL ADHESION KINASE IN HUMAN GASTRIC CARCINOMA CELLS

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Cell migration is a critical event in morphogenesis, tissue repair, and inflammatory reactions. Moreover, it is essential for malignant cells to infiltrate surrounding tissues. Increasing evidence suggests that the interaction of cells with the extracellular matrix affects their migratory properties. Cell migration is regulated by a variety of factors including growth factors such as epidermal growth factors (EGF). Cell adhesion to extracellular matrix molecules is mediated by a family of integrins, each of which is a cell surface protein consisting of an alpha subunit noncovalently associated with a beta subunit. Interaction of integrin with the extracellular matrix activates multiple intracellular signaling pathways, which include stimulation of tyrosine phosphorylation of a 125-kD protein. This protein was termed p125 Focal Adhesion Kinase (FAK), because it is tyrosin kinase located at focal adhesions. However, it remains to be elucidated for a role of FAK and its tyrosine phosphorylation in the formation of focal adhesions. In this present study we examined mechanism by which EGF increases the motility of human gastric carcinoma TMK-1 cells. EGF increased not only the motility of these cells, but also their adhesiveness to the extracellular matrix (type- IV collagen and fibronectin). Further, it increased tyrosine phosphorylation of FAK,which is known to occur during the process of adhesion. Since we have also found that EGF modulate the function of the cadherincatenin system via tyrosine phosphorylation of cadherin associted proteins, EGF may play an important role in the regulation of both interactions of cells with surrounding cells and extracellular matrices.