Role of Anti-Apoptic Aaction of Focal Adhesion Kinase (FAK)

粘着斑激酶(FAK)是一种在多种细胞中表达的酪氨酸激酶，尤其是在浸润性或转移性结肠癌、乳腺癌、口腔癌等癌细胞中表达更明显。FAK在细胞的生长、存活和迁移中起着重要的作用，因此在肿瘤细胞的发展中起着关键作用。FAK是一种酪氨酸磷酸化蛋白，可被蛙皮素、缓激肽、血小板衍生生长因子、肝细胞生长因子、胰岛素、趋化因子等多种刺激所激活。我们发现FAK是被活性氧物种酪氨酸磷酸化的，并且酪氨酸磷酸化是FAK抗细胞凋亡功能的先决条件。此外，PKB/Akt通路参与了FAK的生存信号。我们发现FAK的过表达导致生存通路的结构性激活，并在氧化应激、抗癌药物、辐射诱导的锚定非依赖性细胞iIL-60的凋亡中发挥抗凋亡作用。其他一些蛋白酪氨酸激酶的过度表达和/或失控也会导致结构性下游激酶的激活、无限增殖和致癌转化。我们认为FAK可能像癌基因一样，成为抗癌策略的潜在靶点，特别强调FAK与生存通路的联系。

Focal adhesion kinase (FAK) is a tyrosine kinase expressed in many type of cells, especially in cancer cells such as invasive or metastatic colon carcinomas, breast tumors, oral cancers. FAK plays an important role in cell growth, survival, and migration, thus rendering a critical role in development of tumor cells. FAK is tyrosine-phosphorylated and activated by many types of stimuli, such as bombesin, bradykinin, platelet-derived growth factor, hepatocyte growth factor, insulin, chemokines. We found that FAK is tyrosine-phosphorylated by reactive oxygen species and the tyrosine-phosphorylation was prerequisite for the antiapoptotic function of FAK. In addition, PKB/Akt pathway has been implicated in the survival signal of FAK. We identified that FAK overexpression leads to constitutive activation of survival pathwayand anti-apoptotic role in the apoptosis induced by oxidative stress, anti-cancer drug, irradiation in anchorage-independent cells, IIL-60. Other some protein tyrosine kinase overexpression and/or deregulation also lead to constitutive downstream kinase activation, infinite proliferation and oncogenic transformation. We assumed that FAK may be like an oncogene and become potential targets by anti-cancer strategies, particularly emphasizing the role of FAK linking to survival pathway.