Abstract

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.

Highlights

  • Speaking, epithelia are organized into sheets, tubes, or glandular structures, and perform complex tasks of transporting ions, organic molecules, and water for which specific ion channels/transporters are required

  • SUMMARY AND PERSPECTIVES Epithelial cells are endowed with specific sets of ion channels and transporters that are organized in a polarized fashion specific for the function of the given epithelium

  • Epithelial cells, no doubt due to their high proliferative rate, but perhaps due to their continuously challenged cell volume regulation, walk a thin line between physiology and pathophysiology. That this may endow them with an inherently increased risk of undergoing key events contributing to development of carcinomas

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Summary

Cell volume regulation in epithelial physiology and cancer

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. 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

INTRODUCTION
Findings
ION TRANSPORT AND DRUG RESISTANCE IN CANCER

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