Golubovskaya Vita M, Kweh Frederick A, Cance William G
Department of Surgery, School of Medicine, University of Florida, Gainesville, FL, USA.
Histol Histopathol. 2009 Apr;24(4):503-10. doi: 10.14670/HH-24.503.
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that resides at the sites of integrin clustering, known as focal adhesions. The FAK protein has a molecular mass of 125kDa and is encoded by the FAK gene located on human chromosome 8q24. Structurally, FAK consists of an amino-terminal regulatory FERM domain, a central catalytic kinase domain, two proline-rich motifs, and a carboxy-terminal focal adhesion targeting domain. FAK has been shown to be an important mediator of cell growth, cell proliferation, cell survival and cell migration, all of which are often dysfunctional in cancer cells. Our lab was the first to isolate FAK from primary human tissue and link it to the process of tumorigenesis. We analyzed FAK mRNA expression in normal, invasive and metastatic human tissues and demonstrated through Northern blot analysis that normal tissues had very low levels of FAK mRNA while primary and metastatic tumors significantly overexpressed FAK. We also demonstrated and confirmed FAK overexpression in colorectal carcinoma and liver metastases with real-time PCR. In this review we summarized immunohistochemical data of FAK expression and role in different cancer types tumors and discussed FAK inhibition therapy approaches.
粘着斑激酶(FAK)是一种非受体酪氨酸激酶,定位于整合素聚集的位点,即粘着斑。FAK蛋白的分子量为125kDa,由位于人类染色体8q24上的FAK基因编码。在结构上,FAK由一个氨基末端调节性FERM结构域、一个中央催化激酶结构域、两个富含脯氨酸的基序和一个羧基末端粘着斑靶向结构域组成。FAK已被证明是细胞生长、细胞增殖、细胞存活和细胞迁移的重要介质,而这些过程在癌细胞中往往功能失调。我们实验室是第一个从原发性人类组织中分离出FAK并将其与肿瘤发生过程联系起来的。我们分析了FAK mRNA在正常、侵袭性和转移性人类组织中的表达,并通过Northern印迹分析证明正常组织中FAK mRNA水平非常低,而原发性和转移性肿瘤中FAK明显过表达。我们还通过实时PCR证实了FAK在结直肠癌和肝转移中的过表达。在这篇综述中,我们总结了FAK在不同癌症类型肿瘤中的免疫组化表达数据和作用,并讨论了FAK抑制治疗方法。