Ketogenic HMG-CoA lyase and its product β-hydroxybutyrate promote pancreatic cancer progression

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) tumor cells are deprived of oxygen and nutrients and therefore must adapt their metabolism to ensure proliferation. In some physiological states, cells rely on ketone bodies to satisfy their metabolic needs, especially during nutrient stress. Here, we show that PDA cells can activate ketone body metabolism, and that β-hydroxybutyrate (βOHB) is an alternative cell-intrinsic or systemic fuel that can promote PDA growth and progression. PDA cells activate enzymes required for ketogenesis, utilising various nutrients as carbon sources for ketone body formation. By assessing metabolic gene expression from spontaneously arising PDA tumors in mice, we find HMG-CoA lyase (HMGCL), involved in ketogenesis, to be among the most deregulated metabolic enzymes in P

SUBMITTER: Dr. Gouirand Victoire 

PROVIDER: S-SCDT-EMBOJ-2021-110466 | biostudies-other |

REPOSITORIES: biostudies-other