2019/11/20 by Scott K. Parks, Wolfgang Mueller‐Klieser, Jacques Pouysségur · 1 citation
Biochemistry, Genetics and Molecular Biology · Chemistry · #Cancer, Hypoxia, and Metabolism #Mitochondrial Function and Pathology #ATP Synthase and ATPases Research #Glycolysis #Lactic acid #Oxidative phosphorylation #Gluconeogenesis #Lactic acidosis #Biochemistry #mTORC1 #Intracellular #Tumor microenvironment #Chemistry #Metabolism #Cancer cell #Intracellular pH #Biology #Cancer research #Cell biology #Cancer #Bacteria #Phosphorylation #Tumor cells
paper · pdf · doi:10.1146/annurev-cancerbio-030419-033556
openalex publication_date 2019/11/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/04
Fermentative glycolysis, an ancient evolved metabolic pathway, is exploited by rapidly growing tissues and tumors but also occurs in response to the nutritional and energetic demands of differentiated tissues. The lactic acid it produces is transported across cell membranes through reversible H + /lactate − symporters (MCT1 and MCT4) and is recycled in organs as a major metabolic precursor of gluconeogenesis and an energy source. Concentrations of lactate in the tumor environment, investigated utilizing an induced metabolic bioluminescence imaging (imBI) technique, appear to be dominant biomarkers of tumor response to irradiation and resistance to treatment. Suppression of lactic acid formation by genetic disruption of lactate dehydrogenases A and B in aggressive tumors reactivated OXPHOS (oxidative phosphorylation) to maintain xenograft tumor growth at a halved rate. In contrast, disruption of the lactic acid transporters MCT1/4 suppressed glycolysis, mTORC1, and tumor growth as a result of intracellular acidosis. Furthermore, the global reduction of tumor acidity contributes to activation of the antitumor immune responses, offering hope for future clinical applications.