Using a quantitative systems biology approach we identified 129 genes required for optimal growth under conditions of metabolic acid stress. We have used yeast as a genetic model for metabolic acid stress with the rationale that the metabolic changes that occur in cancer that lead to intracellular acid stress are likely fundamental. Nevertheless, we have only a limited understanding of the consequences of altered intracellular pH on cell physiology, or of the genes and pathways that respond to metabolic acid stress.
To compensate, tumour cells upregulate acid pumps, which expel the metabolic acid into the surrounding tumour environment, resulting in alkalization of intracellular pH and acidification of the tumour microenvironment.
A consequence of the glycolytic phenotype is the accumulation of metabolic acid hence, tumour cells experience considerable intracellular acid stress. A hallmark of all primary and metastatic tumours is their high rate of glucose uptake and glycolysis.
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