Department of Biology, University of Copenhagen Copenhagen, Denmark.
Front Physiol. 2013 Aug 30;4:233. doi: 10.3389/fphys.2013.00233. eCollection 2013.
The physiological function of epithelia is transport of ions, nutrients, and fluid either in secretory or absorptive direction. All of these processes are closely related to cell volume changes, which are thus an integrated part of epithelial function. Transepithelial transport and cell volume regulation both rely on the spatially and temporally coordinated function of ion channels and transporters. In healthy epithelia, specific ion channels/transporters localize to the luminal and basolateral membranes, contributing to functional epithelial polarity. In pathophysiological processes such as cancer, transepithelial and cell volume regulatory ion transport are dys-regulated. Furthermore, epithelial architecture and coordinated ion transport function are lost, cell survival/death balance is altered, and new interactions with the stroma arise, all contributing to drug resistance. Since altered expression of ion transporters and channels is now recognized as one of the hallmarks of cancer, it is timely to consider this especially for epithelia. Epithelial cells are highly proliferative and epithelial cancers, carcinomas, account for about 90% of all cancers. In this review we will focus on ion transporters and channels with key physiological functions in epithelia and known roles in the development of cancer in these tissues. Their roles in cell survival, cell cycle progression, and development of drug resistance in epithelial cancers will be discussed.
上皮细胞的生理功能是将离子、营养物质和液体向分泌或吸收的方向运输。所有这些过程都与细胞体积变化密切相关，因此细胞体积变化是上皮功能的一个组成部分。跨上皮运输和细胞体积调节都依赖于离子通道和转运体的空间和时间协调功能。在健康的上皮细胞中，特定的离子通道/转运体定位于腔侧和基底外侧膜，有助于功能性上皮极性。在癌症等病理生理过程中，跨上皮和细胞体积调节离子转运被失调。此外，上皮结构和协调的离子转运功能丧失，细胞存活/死亡平衡改变，与基质的新相互作用出现，所有这些都导致了耐药性。由于离子转运体和通道的表达改变现在被认为是癌症的特征之一，因此及时考虑上皮细胞尤其重要。上皮细胞具有高度的增殖能力，上皮癌（carcinoma）约占所有癌症的 90%。在这篇综述中，我们将重点介绍在上皮细胞中具有关键生理功能并在这些组织的癌症发展中具有已知作用的离子转运体和通道。我们将讨论它们在上皮癌细胞中的存活、细胞周期进展和耐药性发展中的作用。
