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整合素在细胞迁移和侵袭中的作用及调控

The role and regulation of integrins in cell migration and invasion.

作者信息

Chastney Megan R, Kaivola Jasmin, Leppänen Veli-Matti, Ivaska Johanna

机构信息

Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.

Department of Life Technologies, University of Turku, Turku, Finland.

出版信息

Nat Rev Mol Cell Biol. 2025 Feb;26(2):147-167. doi: 10.1038/s41580-024-00777-1. Epub 2024 Sep 30.

Abstract

Integrin receptors are the main molecular link between cells and the extracellular matrix (ECM) as well as mediating cell-cell interactions. Integrin-ECM binding triggers the formation of heterogeneous multi-protein assemblies termed integrin adhesion complexes (IACs) that enable integrins to transform extracellular cues into intracellular signals that affect many cellular processes, especially cell motility. Cell migration is essential for diverse physiological and pathological processes and is dysregulated in cancer to favour cell invasion and metastasis. Here, we discuss recent findings on the role of integrins in cell migration with a focus on cancer cell dissemination. We review how integrins regulate the spatial distribution and dynamics of different IACs, covering classical focal adhesions, emerging adhesion types and adhesion regulation. We discuss the diverse roles integrins have during cancer progression from cell migration across varied ECM landscapes to breaching barriers such as the basement membrane, and eventual colonization of distant organs.

摘要

整合素受体是细胞与细胞外基质(ECM)之间的主要分子连接,同时也介导细胞间相互作用。整合素与ECM的结合触发了称为整合素黏附复合体(IACs)的异质多蛋白组装体的形成,使整合素能够将细胞外信号转化为影响许多细胞过程的细胞内信号,尤其是细胞运动。细胞迁移对于多种生理和病理过程至关重要,并且在癌症中失调,从而促进细胞侵袭和转移。在这里,我们讨论整合素在细胞迁移中的作用的最新发现,重点是癌细胞的扩散。我们回顾整合素如何调节不同IACs的空间分布和动态,涵盖经典的黏着斑、新兴的黏附类型和黏附调节。我们讨论整合素在癌症进展过程中的多种作用,从细胞在不同ECM环境中的迁移到突破诸如基底膜等屏障,以及最终在远处器官的定植。

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