PPARδ Orchestrates a Prometastatic Metabolic Response to Microenvironmental Cues in Pancreatic Cancer.

ABSTRACT: The pronounced desmoplastic response in pancreatic ductal adenocarcinoma (PDAC) contributes to the development of a microenvironment depleted of oxygen and nutrients. To survive in this hostile environment, PDAC cells use various adaptive mechanisms that may represent therapeutic targets. In this study, we showed that nutrient starvation and microenvironmental signals commonly present in PDAC tumors activate PPARδ to rewire cellular metabolism and promote invasive and metastatic properties both in vitro and in vivo. Mild mitochondrial inhibition induced by low-dose etomoxir or signals from tumor-associated macrophages altered the lipidome and triggered the downstream transcriptional program of PPARδ. Specifically, PPARδ reduced mitochondrial oxygen consumption and boosted the glycolytic ca

SUBMITTER: Parejo-Alonso B 

PROVIDER: S-EPMC12402788 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature