Audero, M.M.; Prevarskaya, N.; Fiorio Pla, A. Ca2+ Signalling and Hypoxia/Acidic Tumour Microenvironment Interplay in Tumour Progression. Int. J. Mol. Sci.2022, 23, 7377.
Audero, M.M.; Prevarskaya, N.; Fiorio Pla, A. Ca2+ Signalling and Hypoxia/Acidic Tumour Microenvironment Interplay in Tumour Progression. Int. J. Mol. Sci. 2022, 23, 7377.
Abstract
Solid tumours are characterized by an altered microenvironment (TME) from the physi-cochemical point of view, displaying a highly hypoxic and acidic interstitial fluid. Hy-poxia results from uncontrolled proliferation, aberrant vascularization and altered can-cer cell metabolism. Tumour cellular apparatus adapt to hypoxia by altering its metab-olism and behaviour, increasing its migratory and metastatic abilities by acquisition of a mesenchymal phenotype and selection of aggressive tumour cell clones. Extracellular acidosis is considered a cancer hallmark, acting as a driver of cancer aggressiveness by promoting tumour metastasis and chemoresistance by selecting for more aggressive cell phenotypes, although the underlying mechanism is still not clear. In this context, Ca2+ channels represent good target candidates due to their ability to integrate signals from the TME. Ca2+ channels are pH and hypoxia sensors and alterations in Ca2+ homeostasis in cancer progression and vascularization have been extensively reported. The present review will focus on Ca2+ permeable ion channels, with a major focus on TRP, SOC and PIEZO channels, that are modulated by tumour hypoxia and acidosis as well as the role of the resulted altered Ca2+ signals on cancer progression hallmarks. A deeper compre-hension of the Ca2+ signaling and acidic pH/hypoxia interplay will break new ground for the discovery of alternative and attractive therapeutics targets.
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