《生命科学》 2020, 32(1): 1-8

不同亚细胞定位的黏着斑激酶对肿瘤的调控机制

季　嫱，马玉泽，郝慧芳*，王志钢

(内蒙古大学生命科学学院，呼和浩特 010070)

摘　要：

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。

Roles of focal adhesion kinase in distinct subcellular locations on tumor regulation

JI Qiang， MA Yu-Ze， HAO Hui-Fang*， WANG Zhi-Gang

(College of Life Sciences， Inner Mongolia University， Hohhot 010070， China)

Abstract:

Abstract: 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.