Abstract
Background Cancer 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.
Highlights
Cancer progression occurs upon mutations on regulatory genes that control biological functions including cellular bioenergetics
Using breast cancer cells as a model system, we found that extracellular lactate promotes a significant effect on cell survival under nutrient stress conditions where glucose or glutamine is limited
Our data showed that lactate metabolism increased ROS production, due to a switch toward oxidative phosphorylation, which signaled cells to produce NADPH and initiate glutathione production from the lactate-derived amino acids glutamate, glycine, and cysteine
Summary
Cancer 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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
