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Shear stress stimulates integrin β1 trafficking and increases directional migration of cancer cells via promoting deacetylation of microtubules.

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机构： [a]Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China [b]Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu 610072, Sichuan, PR China [c]Center for Information in Biology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China [d]The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, PR China [e]Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong, PR China

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关键词： Integrin internalization and recycling Caveolin-1 Focal adhesion turnover Microtubule deacetylation HDAC6

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In egress routes of malignancy, cancer cells are constantly subjected to shear stress imposed by blood/lymph flow. Increasing evidence points toward the regulatory roles of shear stress in tumor cell adhesion and motility. Although it is known that integrin endocytic trafficking governs focal adhesion (FA) turnover and cell migration, the effect and biological consequences of low shear stress (LSS) on integrin trafficking remain unclear. Here, we identified the critical role of integrin β1 trafficking and caveolin-1 (Cav-1) mediated endocytosis in LSS-induced cell directional migration. LSS altered the distribution of integrin β1 in MDA-MB-231 cells and significantly promoted its internalization and recycling, which in turn facilitated FA turnover and directional cell migration. Furthermore, LSS induced cytoskeleton remodeling, which was required for internalization of integrin β1. LSS down-regulated the acetylation level of microtubules (MTs) via activating ROCK/HDAC6 pathway, resulting in elevation of MTs dynamics, Cav-1 motility, and Cav-1-dependent integrin β1 recycling. We also showed that high HDAC6 expression was a ROCK-dependent prognostic factor, which was correlated with poor outcomes in breast cancer patients. Taken together, these results defined a novel mechanism by which LSS enhanced integrin β1 trafficking via actin cytoskeleton remodeling and ROCK/HDAC6 mediated deacetylation of MTs, thereby promoting FAs turnover and directional cell migration. Copyright © 2020 Elsevier B.V. All rights reserved.

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出版当年[2020]版：

大类 | 2 区生物学

小类 | 3 区生化与分子生物学 3 区细胞生物学

最新[2023]版：

大类 | 2 区生物学

小类 | 3 区生化与分子生物学 3 区细胞生物学

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第一作者机构： [a]Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China

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通讯机构： [a]Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China [b]Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu 610072, Sichuan, PR China [*1]School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, PR China. [*2]Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, PR China.

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