Extracellular lactate cooperates with limited glucose and glutamine to sustain breast cancer cell survival by providing ATP, NADPH, amino acids, and glutathione

Abstract

BackgroundCancer progression occurs upon mutations on regulatory genes that control biological functions including cellular bioenergetics. Such perturbations lead to a metabolic switch that favors aerobic glycolysis and lactate production over oxidative phosphorylation. This process is known as the Warburg effect and results in a lactate-rich tumor microenvironment. The apparently wasteful mechanism has raised the question of why cancer cells switch from the high ATP producing TCA cycle/OXPHOS to glycolysis; and whether lactate serves a biological function in energy metabolism since a high lactate environment correlates with worse patient prognosis in several malignancies including breast cancer. Our goals were to first, determine the fate of carbons from lactate in breast cancer cells; and second, determine the mechanism of lactate metabolism.Materials and methodsIn the current study we used several assays including: survival assay under nutrient stress conditions, NMR spectroscopy, m ...