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

EGF对人胃癌细胞细胞-基质相互作用及p125粘着激酶酪氨酸磷酸化的影响

基本信息

批准号：
06672216
负责人：
ITO Fumiaki
金额：
$ 1.34万
依托单位：
SETSUNAN UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

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.

细胞迁移是形态发生、组织修复和炎症反应中的关键事件。此外，恶性细胞浸润周围组织是必要的。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。细胞迁移受多种因子调节，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由整合素家族介导，每个整合素家族是由与β亚基非共价结合的α亚基组成的细胞表面蛋白。整合素与细胞外基质的相互作用激活多种细胞内信号传导途径，包括刺激125-kD蛋白的酪氨酸磷酸化。这种蛋白被称为p125粘着斑激酶（FAK），因为它是位于粘着斑的酪氨酸激酶。然而，FAK及其酪氨酸磷酸化在粘着斑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，而且增加了它们对细胞外基质（IV型胶原和纤连蛋白）的粘附。此外，它增加了FAK的酪氨酸磷酸化，这是已知的粘附过程中发生的。由于我们还发现EGF通过cadherin相关蛋白的酪氨酸磷酸化来调节cadherincatenin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起重要作用。