摘要
黏着斑激酶(focal adhesion kinase, FAK)是一种非受体蛋白酪氨酸激酶。在细胞质黏着斑中,FAK通过调控细胞黏着斑的解聚与组装及多个蛋白质的磷酸化从而调节细胞的增殖和迁移。FAK也定位于细胞核和内体中。在细胞核中,FAK可导致p53的多聚泛素化及降解,从而影响正常细胞的存活和肿瘤细胞的生长。此外,核FAK还能够通过调节细胞因子和趋化因子的表达促进肿瘤免疫逃逸的发生。在内体中,FAK通过FERM结构域定位到内体并被激活。内体中整合素的信号转导时间比质膜上持续的时间更长,并且能够阻止肿瘤细胞发生失巢凋亡,因此,内体FAK可通过抵抗失巢凋亡促进肿瘤细胞的转移。现就不同亚细胞定位的FAK对肿瘤发生和发展的调控作用及机制进行讨论。
Focal adhesion kinase(FAK) is a non-receptor protein-tyrosine kinase. In cytoplasmic focal adhesions, FAK regulates the disassembly and assembly of focal adhesion and the phosphorylation of multiple proteins to regulate cell proliferation and migration. FAK is also located in the nucleus and endosome. In the nucleus, FAK leads to the ubiquitination of p53 and its subsequently degradation, thereby affecting the survival of normal cells and the growth of tumor cells. In addition, nuclear FAK can also promote the occurrence of tumor immune escape by regulating the expression of cytokines and chemokines. In the endosome, the FERM domain of FAK decides its localizations and activation. Integrins in the endosome last longer than those on the plasma membrane, and can prevent the anoikis of tumor cells. Therefore, FAK in the endosome promotes the metastasis of tumor cells by regulating anoikis-resistance of tumor cells. This paper reviews the roles of FAK on tumorigenesis and progression in different subcellular locations.
作者
季嫱
马玉泽
郝慧芳
王志钢
JI Qiang;MA Yu-Ze;HAO Hui-Fang;WANG Zhi-Gang(College of Life Sciences,Inner Mongolia University,Hohhot 010070,China)
出处
《生命科学》
CSCD
北大核心
2020年第1期1-8,共8页
Chinese Bulletin of Life Sciences
基金
国家自然科学基金项目(31860309,31760675)
内蒙古自治区自然科学基金博士基金项目(2016BS0304)
内蒙古自治区留学归国人员启动项目(12000-12101014)
内蒙古大学高层次人才引进科研项目(135130)。
关键词
黏着斑激酶
亚细胞定位
细胞核
内体
肿瘤
focal adhesion kinase(FAK)
subcellular locations
nucleus
endosomes
tumor
