Multiple effects of intracellular pH modulation in cancer cells

Cancer cells adapt to a decreased oxygen tension by turning to anaerobic respiration and secreting lactic acid, thus a hallmark of solid tumors are hypoxia and the consequent upregulation of specific hypoxia inducible factors. Reversed pH is also a peculiar feature of cancer cells, being their extracellular microenvironment acid while the intracellular basic. The elucidation of the molecular determinants of tumor microenvironment as well as the identification of the crucial factors present in the extracellular matrix could be instrumental to develop new approaches for modulate cancer cells metabolism. Moreover, the manipulation of intracellular pH could influence the signaling pathways governing the survival of cancer cells.