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离子通道构象调节整合素依赖的信号转导。

Ion Channel Conformations Regulate Integrin-Dependent Signaling.

机构信息

Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milano, Italy.

Department of Experimental and Clinical Medicine, University of Florence, 50134 Firenze, Italy.

出版信息

Trends Cell Biol. 2019 Apr;29(4):298-307. doi: 10.1016/j.tcb.2018.12.005. Epub 2019 Jan 8.

Abstract

Cell-matrix adhesion determines the choice between different cell fates and is accompanied by substantial changes in ion transport. The greatest evidence is the bidirectional interplay occurring between integrin receptors and K channels. These proteins can form signaling hubs that regulate cell proliferation, differentiation, and migration in normal and neoplastic tissue. Recent results show that the physical interaction with integrins determines the balance of the open and closed K channel states, and individual channel conformations regulate distinct downstream pathways. We propose a model of how these mechanisms regulate proliferation and metastasis in cancer cells. In particular, we suggest that the neoplastic progression could be modulated by targeting specific ion channel conformations.

摘要

细胞-基质黏附决定了不同细胞命运的选择,并伴随着离子转运的显著变化。最大的证据是整合素受体和 K 通道之间发生的双向相互作用。这些蛋白质可以形成信号枢纽,调节正常和肿瘤组织中的细胞增殖、分化和迁移。最近的结果表明,与整合素的物理相互作用决定了开放和关闭 K 通道状态的平衡,而单个通道构象调节不同的下游途径。我们提出了一个模型,说明这些机制如何调节癌细胞的增殖和转移。特别是,我们建议通过靶向特定的离子通道构象来调节肿瘤的进展。

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