Dysregulated pH: a perfect storm for cancer progression

Abstract

Dysregulated pH is emerging as a hallmark of cancer because cancers have a 'reversed' pH gradient, with a constitutively increased intracellular pH that is higher than the extracellular pH. This Perspective highlights the central role of pH sensor proteins in facilitating the adaptations that occur in cancer cells. Although cancer is a diverse set of diseases, cancer cells share a number of adaptive hallmarks. Dysregulated pH is emerging as a hallmark of cancer because cancers show a 'reversed' pH gradient with a constitutively increased intracellular pH that is higher than the extracellular pH. This gradient enables cancer progression by promoting proliferation, the evasion of apoptosis, metabolic adaptation, migration and invasion. Several new advances, including an increased understanding of pH sensors, have provided insight into the molecular basis for pH-dependent cell behaviours that are relevant to cancer cell biology. We highlight the central role of pH sensors in cancer cell adaptations and suggest how dysregulated pH could be exploited to develop cancer-specific therapeutics.