Integrin-regulated FAK-Src signaling in normal and cancer cells
Integrin-regulated FAK-Src signaling in normal and cancer cells
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DOI：
10.1016/j.ceb.2006.08.011
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发表时间：
2006-10-01
影响因子：
7.5
通讯作者：
Schlaepfer, David D.
中科院分区：
文献类型：
--
作者：
Mitra, Satyajit K.;Schlaepfer, David D.
整合素可以通过募集和激活信号传导蛋白如非受体酪氨酸激酶（包括粘着斑激酶（FAK）和形成双激酶复合物的c-Src）来改变细胞行为。FAK-Src复合物结合并可磷酸化各种衔接蛋白，如p130 Cas和桩蛋白。在正常细胞中，存在多个整合素调节的连接以激活FAK或Src。活化的FAKSrc功能是促进细胞运动、细胞周期进展和细胞存活。最近的研究发现，FAK-Src复合物在许多肿瘤细胞中被激活，并产生导致肿瘤生长和转移的信号。由于FAK和Src的催化活性在促进VEGF相关的肿瘤血管生成和蛋白酶相关的肿瘤转移中是重要的，因此越来越多的人支持FAK和Src可能是抑制肿瘤进展的治疗相关靶点。
Integrins can alter cellular behavior through the recruitment and activation of signaling proteins such as non-receptor tyrosine kinases including focal adhesion kinase (FAK) and c-Src that form a dual kinase complex. The FAK-Src complex binds to and can phosphorylate various adaptor proteins such as p130Cas and paxillin. In normal cells, multiple integrin-regulated linkages exist to activate FAK or Src. Activated FAKSrc functions to promote cell motility, cell cycle progression and cell survival. Recent studies have found that the FAK-Src complex is activated in many tumor cells and generates signals leading to tumor growth and metastasis. As both FAK and Src catalytic activities are important in promoting VEGF-associated tumor angiogenesis and protease-associated tumor metastasis, support is growing that FAK and Src may be therapeutically relevant targets in the inhibition of tumor progression.