Uridine-derived ribose fuels glucose-restricted pancreatic cancer.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is a lethal disease notoriously resistant to therapy^1,2. This is mediated in part by a complex tumour microenvironment³, low vascularity⁴, and metabolic aberrations^5,6. Although altered metabolism drives tumour progression, the spectrum of metabolites used as nutrients by PDA remains largely unknown. Here we identified uridine as a fuel for PDA in glucose-deprived conditions by assessing how more than 175 metabolites impacted metabolic activity in 21 pancreatic cell lines under nutrient restriction. Uridine utilization strongly correlated with the expression of uridine phosphorylase 1 (UPP1), which we demonstrate liberates uridine-derived ribose to fuel central carbon metabolism and thereby support redox bal

SUBMITTER: Nwosu ZC 

PROVIDER: S-EPMC10232363 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature