整合素活化及其介导的黏着斑成熟与肿瘤转移
黄梦汶¹, 林昶东¹, 陈剑峰^1,2,*
1细胞生物学国家重点实验室，中国科学院分子细胞科学卓越创新中心，中国科学院上海生物化学与细胞生物学研究所，中国科学院大学，上海 200031；²中国科学院大学杭州高等研究院生命与健康科学学院，杭州 310024
摘要
整合素是一类由α和β两个亚基组成的异源二聚体单次跨膜细胞黏附分子，通过与其对应配体相互作用，介导细胞与细胞、细胞与胞外基质之间的黏附，同时可以将细胞外信号传递至胞内，并招募一系列胞内蛋白与整合素胞内段结合，在细胞膜上形成超分子结构，激活下游信号。整合素的活化进程伴随着其胞外结构域由折叠构象转变为伸展构象以及胞内结构域的彼此分离。在细胞迁移过程中，整合素参与黏着斑的形成，连接胞外基质和细胞骨架，传递胞内-胞外的力学信号驱使细胞迁移。肿瘤微环境介导的整合素活化可促进多种类型细胞向肿瘤部位迁移，共同实现血管生成及肿瘤转移。本文对整合素的活化过程，其介导黏着斑动态变化引发的细胞迁移及对肿瘤转移的影响进行综述。
关键词： 整合素; 活化; 黏着斑; 细胞迁移; 血管生成
分类号：R363

Integrin activation, focal adhesion maturation and tumor metastasis
HUANG Meng-Wen¹, LIN Chang-Dong¹, CHEN Jian-Feng^1,2,*
1State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China；²School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China
Abstract
Integrins are a large family of heterodimeric cell adhesion molecules composed of α and β subunits. Through interaction with their specific ligands, integrins mediate cell-cell and cell-extracellular matrix interactions. Via outside-in signaling, integrins can recruit cytoplasmic proteins to their intracellular domains and then cluster into supramolecular structures and trigger downstream signaling. Integrin activation is associated with a global conformation rearrangement from bent to extended in ectodomains and the separation of α and β subunit cytoplasmic domains. During cell migration, integrins regulate the focal adhesion dynamics and transmit forces between the extracellular matrix and the cell cytoskeleton. In tumor microenvironment, integrins on multiple kinds of cells could be activated, which modulates cell migration into tumor and contributes to angiogenesis and tumor metastasis. Here, we review the mechanism of integrin activation, dynamics of focal adhesions during cell migration and tumor metastasis.


Key words: integrin; activation; focal adhesion; cell migration; angiogenesis

收稿日期：2020-07-03　　录用日期：2021-04-02
通讯作者：陈剑峰　　E-mail: jfchen@sibcb.ac.cn
DOI: 10.13294/j.aps.2021.0023
引用本文：
黄梦汶, 林昶东, 陈剑峰. 整合素活化及其介导的黏着斑成熟与肿瘤转移[J]. 生理学报 2021; 73 (2): 151-159.
HUANG Meng-Wen, LIN Chang-Dong, CHEN Jian-Feng. Integrin activation, focal adhesion maturation and tumor metastasis. Acta Physiol Sin 2021; 73 (2): 151-159 (in Chinese with English abstract).



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