容积调节性和钙激活阴离子通道在细胞容积稳态、癌症及耐药性中的作用
Role of volume-regulated and calcium-activated anion channels in cell volume homeostasis, cancer and drug resistance.
作者信息
Hoffmann Else K, Sørensen Belinda H, Sauter Daniel P R, Lambert Ian H
机构信息
a Department of Biology ; Section for Cell Biology and Physiology; University of Copenhagen ; Copenhagen , Denmark.
出版信息
Channels (Austin). 2015;9(6):380-96. doi: 10.1080/19336950.2015.1089007. Epub 2015 Nov 16.
Abstract
Volume-regulated channels for anions (VRAC) / organic osmolytes (VSOAC) play essential roles in cell volume regulation and other cellular functions, e.g. proliferation, cell migration and apoptosis. LRRC8A, which belongs to the leucine rich-repeat containing protein family, was recently shown to be an essential component of both VRAC and VSOAC. Reduced VRAC and VSOAC activities are seen in drug resistant cancer cells. ANO1 is a calcium-activated chloride channel expressed on the plasma membrane of e.g., secretory epithelia. ANO1 is amplified and highly expressed in a large number of carcinomas. The gene, encoding for ANO1, maps to a region on chromosome 11 (11q13) that is frequently amplified in cancer cells. Knockdown of ANO1 impairs cell proliferation and cell migration in several cancer cells. Below we summarize the basic biophysical properties of VRAC, VSOAC and ANO1 and their most important cellular functions as well as their role in cancer and drug resistance.
摘要
阴离子（VRAC）/有机渗透溶质（VSOAC）的容积调节通道在细胞容积调节和其他细胞功能中发挥着重要作用，例如增殖、细胞迁移和凋亡。LRRC8A属于富含亮氨酸重复序列的蛋白质家族，最近被证明是VRAC和VSOAC的重要组成部分。在耐药癌细胞中可见VRAC和VSOAC活性降低。ANO1是一种钙激活氯离子通道，例如在分泌上皮的质膜上表达。ANO1在大量癌组织中扩增并高表达。编码ANO1的基因定位于染色体11（11q13）上的一个区域，该区域在癌细胞中经常扩增。敲低ANO1会损害几种癌细胞的细胞增殖和细胞迁移。下面我们总结VRAC、VSOAC和ANO1的基本生物物理特性、它们最重要的细胞功能以及它们在癌症和耐药性中的作用。
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