Suppression of the KRAS-NRF2 axis shifts arginine into the phosphocreatine energy system in pancreatic cancer cells.

ABSTRACT: In pancreatic ductal adenocarcinomas (PDAC), the KRAS^G12D-NRF2 axis controls cellular functions such as redox homeostasis and metabolism. Disruption of this axis through suppression of NRF2 leads to profound reprogramming of metabolism. Unbiased transcriptome and metabolome analyses showed that PDAC cells with disrupted KRAS^G12D-NRF2 signaling (NRF2^-/- cells) shift from aerobic glycolysis to metabolic pathways fed by amino acids. Metabolome, RNA-seq and qRT-PCR analyses revealed a blockade of the urea cycle, making NRF2^-/- cells dependent on exogenous arginine for survival. Arginine is channeled into anabolic pathways, including the synthesis of phosphocreatine, which generates an energy buffer ess

SUBMITTER: Di Giorgio E 

PROVIDER: S-EPMC10746371 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature