biostudies-literatureBenitz SNational Cancer Institute (NCI)Deutsche Forschungsgemeinschaft (DFG)Sky Foundation (THE SKY FOUNDATION)Sky FoundationDeutsche ForschungsgemeinschaftNational Cancer InstituteDeutsche KrebshilfeNCI NIH HHSDeutsche Krebshilfe (German Cancer Aid)2162-2182https://www.ebi.ac.uk/biostudies/studies/S-EPMC11528200biostudies-literatureUnknown14(11)Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells into precancerous lesions, to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We discovered that normal acinar cell differentiation, maintained by the transcription factor PDX1, suppresses a broad gastric cell identity that is maintained in metaplasia, neoplasia, and the classical subtype of PDAC in a mouse and human. We identified the receptor tyrosine kinase ROR2 as marker of a gastric metaplasia-like identity in pancreas neoplasms. Ablation of Ror2 in a mouse model of pancreatic tumorigenesis promoted a switch to a gastric pit cell identity that largely persisted through progression to the classical subtype of PDAC. In bCancer discoveryROR2 Regulates Cellular Plasticity in Pancreatic Neoplasia and Adenocarcinoma.PMC115282001F31CA271576R01 CA247516U01 CA274154BE 7224/1-1U01CA224145R00 CA263154U01 CA224145F31 CA271576R00CA26315470115409P30 CA045508U01CA274154R01CA247516MA 4115/3-1Metzler TBenitz SZwernik SSteep ABednar FMahajan UMDavis ETHuang LSalas-Escabillas DJPreall JTheisen BKSong LLouw MRempinski DMcQuithey HWen HJZhang ZBrender SMLong DWRegel ISteele NGCrawford HCNasser MMLoveless IfalseROR2 Regulates Cellular Plasticity in Pancreatic Neoplasia and Adenocarcinoma.Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells into precancerous lesions, to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We discovered that normal acinar cell differentiation, maintained by the transcription factor PDX1, suppresses a broad gastric cell identity that is maintained in metaplasia, neoplasia, and the classical subtype of PDAC in a mouse and human. We identified the receptor tyrosine kinase ROR2 as marker of a gastric metaplasia-like identity in pancreas neoplasms. Ablation of Ror2 in a mouse model of pancreatic tumorigenesis promoted a switch to a gastric pit cell identity that largely persisted through progression to the classical subtype of PDAC. In b2024-01-01T00:00:00Z2024 Nov2026-07-16T00:25:46.508Z2025-04-04T22:47:41.827ZS-EPMC115282003897588610.1158/2159-8290.CD-24-0137