School of Biological Sciences, University of Reading, Reading, Berkshire RG6 6UR, United Kingdom.
School of Biological Sciences, University of Reading, Reading, Berkshire RG6 6UR, United Kingdom.
Exp Cell Res. 2018 Sep 15;370(2):417-425. doi: 10.1016/j.yexcr.2018.07.005. Epub 2018 Jul 9.
Focal adhesions (FAs) play an important role in cancer cell migration and metastasis by linking the actin cytoskeleton to the extracellular matrix, allowing the cell to generate traction. SUMOylation is a post-translational modification of proteins on lysine residues that can affect protein localisation, turnover and protein-protein interactions. In this study, we demonstrate that talin, a key component of FAs, can be post-translationally modified by SUMOylation in MDA-MB-231 breast cancer cells and U2OS osteosarcoma cells. Furthermore we demonstrate that SUMOylation regulates the dynamic activities of FAs including their number, size and turnover rate. Inhibiting SUMOylation significantly reduced the speed of cell migration. The identification of talin as a SUMO target provides insight into the mechanisms regulating focal adhesion formation and turnover and potentially identifies a novel mechanism underlying cell migration.
焦点黏附(FAs)通过将肌动蛋白细胞骨架连接到细胞外基质,使细胞产生牵引力,从而在癌细胞迁移和转移中发挥重要作用。SUMOylation 是赖氨酸残基上蛋白质的翻译后修饰,可以影响蛋白质的定位、周转和蛋白质-蛋白质相互作用。在这项研究中,我们证明了 FA 的关键组成部分 talin 可以在 MDA-MB-231 乳腺癌细胞和 U2OS 骨肉瘤细胞中通过 SUMOylation 进行翻译后修饰。此外,我们还证明了 SUMOylation 调节 FA 的动态活动,包括它们的数量、大小和周转率。抑制 SUMOylation 显著降低了细胞迁移的速度。Talin 作为 SUMO 靶标的鉴定提供了对调节焦点黏附形成和周转的机制的深入了解,并可能为细胞迁移确定了一种新的机制。