Dual Role of NRF2 in Pancreatic Precursor Lesions.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) arises from distinct precursor lesions, primarily pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). Unlike PanIN, IPMN is a cystic lesion detectable by imaging, providing an opportunity for early intervention. However, the molecular determinants guiding the formation of PanIN versus IPMN remain poorly understood. In this study, we uncover a previously unrecognized role for nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of redox homeostasis, in dictating pancreatic precursor lesion fate. Although NRF2 is known to promote PanIN formation and sustain PDA, we found that active NRF2 levels are significantly lower in human IPMN compared with PanIN and PDA. Using a conditional NRF2 knocko

SUBMITTER: Ichimiya S 

PROVIDER: S-EPMC12158068 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature