Metabolic priming by multiple enzyme systems supports glycolysis, HIF1α stabilisation, and human cancer cell survival in early hypoxia

ABSTRACT: Adaptation to chronic hypoxia occurs through changes in protein expression, which are controlled by hypoxia inducible factor 1α (HIF1α) and are necessary for cancer cell survival. However, the mechanisms that enable cancer cells to adapt in early hypoxia, before the HIF1α-mediated transcription programme is fully established, remain poorly understood. Here we show in human breast cancer cells, that within 3 hours of hypoxia exposure, glycolytic flux increases in a HIF1α-independent manner but is limited by NAD+ availability. Glycolytic ATP maintenance and cell survival in early hypoxia rely on reserve lactate dehydrogenase A capacity as well as the activity of glutamate-oxoglutarate transaminase 1 (GOT1), an enzyme that fuels malate dehydrogenase 1 (MDH1)-derived NAD+. Additionally, GOT1 m

SUBMITTER: Dr. Dimitrios Anastasiou 

PROVIDER: S-SCDT-10_1038-S44318-024-00065-W | biostudies-other |

REPOSITORIES: biostudies-other