pH-channeling in cancer: How pH-dependence of cation channels shapes cancer pathophysiology

Pethő, Zoltán; Najder, Karolina; Carvalho, Tiago; McMorrow, Roisin; Todesca, Luca Matteo; Rugi, Micol; Bulk, Etmar; Chan, Alan; Löwik, Clemens W. G. M.; Reshkin, Stephan J.; Schwab, Albrecht

Abstract

Tissue acidosis plays a pivotal role in tumor progression: in particular, interstitial acidosis promotes tumor cell invasion, and is a major contributor to the dysregulation of tumor immunity and tumor stromal cells. The cell membrane and integral membrane proteins commonly act as important sensors and transducers of altered pH. Cell adhesion molecules and cation channels are prominent membrane proteins, the majority of which is regulated by protons. The pathophysiological consequences of proton-sensitive ion channel function in cancer, however, are scarcely considered in the literature. Thus, the main focus of this review is to highlight possible events in tumor progression and tumor immunity where the pH sensitivity of cation channels could be of great importance.