Pyruvate Kinase Activity Regulates Cystine Starvation Induced Ferroptosis through Malic Enzyme 1 in Pancreatic Cancer Cells.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with high mortality and limited efficacious therapeutic options. PDAC cells undergo metabolic alterations to survive within a nutrient-depleted tumor microenvironment. One critical metabolic shift in PDAC cells occurs through altered isoform expression of the glycolytic enzyme, pyruvate kinase (PK). Pancreatic cancer cells preferentially upregulate pyruvate kinase muscle isoform 2 isoform (PKM2). PKM2 expression reprograms many metabolic pathways, but little is known about its impact on cystine metabolism. Cystine metabolism is critical for supporting survival through its role in defense against ferroptosis, a non-apoptotic iron-dependent form of cell death characterized by unchecked lipid peroxidation. To improve our understa

SUBMITTER: Ensink E 

PROVIDER: S-EPMC10516027 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature