Abstract 100: Pancreatic cancer cells rely on the NADPH producing enzyme, IDH1, for adaptive survival against acute metabolic stress

We recently demonstrated that pancreatic cancer cells adapt to low nutrient conditions and chemotherapeutic stress through an adaptive response where HuR (ELAVL1) protects cells from oxidative damage induced by metabolic stress. RNA sequencing data and a series of protein-RNA interaction assays proved that HuR stabilizes transcript levels of the NADPH producing enzyme, isocitrate dehydrogenase 1 (IDH1). HuR-knockout cells had near-complete loss of IDH1 expression (manuscript under review). In light of the fact that IDH1-null mice are particularly sensitive to oxidative damage, we hypothesize that this enzyme plays a critical role in PDA survival of acute stress. We examined the expression levels of all eight well-characterized NADPH-generating enzymes in pancreatic cancer cells in vitro, and demonstrate that only IDH1 and phosphogluconate dehydrogenase (PGD) are upregulated by >2-fold after incubation in low glucose (5 mM) for 48 hours. IDH1-knockout MiaPaCa2 cells were generated through CRISPR gene editing, such that mRNA expression was detected at Citation Format: Ali Vaziri-Gohar, Mahsa Zarei, Jonathan R. Brody, Jordan M. Winter. Pancreatic cancer cells rely on the NADPH producing enzyme, IDH1, for adaptive survival against acute metabolic stress [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 100. doi:10.1158/1538-7445.AM2017-100