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

细胞迁移是形态发生、组织修复和炎症反应的关键事件。此外，恶性细胞浸润周围组织是必不可少的。越来越多的证据表明，细胞与细胞外基质的相互作用影响其迁移特性。细胞迁移受多种因素的调控，包括生长因子，如表皮生长因子（EGF）。细胞与细胞外基质分子的粘附是由一个整合素家族介导的，每个整合素家族都是由一个α亚基与一个β亚基非共价结合而成的细胞表面蛋白。整合素与细胞外基质的相互作用激活了多种细胞内信号通路，其中包括刺激125-kD蛋白的酪氨酸磷酸化。该蛋白被命名为p125局灶黏附激酶（FAK），因为它是位于局灶黏附的酪氨酸激酶。然而，FAK及其酪氨酸磷酸化在局灶粘连形成中的作用仍有待阐明。在本研究中，我们研究了EGF增加人胃癌TMK-1细胞运动的机制。EGF不仅增加了这些细胞的运动性，还增加了它们对细胞外基质（IV型胶原和纤维连接蛋白）的粘附性。此外，它增加了FAK的酪氨酸磷酸化，这是在粘附过程中发生的。由于我们还发现EGF通过酪氨酸磷酸化钙粘连蛋白相关蛋白来调节钙粘连蛋白系统的功能，因此EGF可能在调节细胞与周围细胞和细胞外基质的相互作用中发挥重要作用。

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.