p53 mediates persistent Stat3 activation and contributes to stromal reprogramming in pancreatic cancer in humans and mice

Background: Stromal reprogramming rather than stromal depletion is emerging as potential major target in patients with pancreatic ductal adenocarcinoma (PDAC). Increasing evidence suggests that persistent signal transducer and activator of transcription 3 (Stat3) activation is involved in the progression of various solid cancers. We hypothesize that functional loss of p53 mediates a new persistent activation-dependent key mechanism in stromal reprogramming through Stat3. Methods: Various genetically engineered mouse models of pancreatic cancer based on the LSL-Kras G12D knock-in were created. Stat3 expression, p…