ROR2 regulates cellular plasticity in pancreatic neoplasia and adenocarcinoma.

Benitz, Simone, Steep, Alexander, Nasser, Malak, Preall, Jonathan, Mahajan, Ujjwal M, McQuithey, Holly, Loveless, Ian, Davis, Erick T, Wen, Hui-Ju, Long, Daniel W, Metzler, Thomas, Zwernik, Samuel, Louw, Michaela, Rempinski, Donald, Salas-Escabillas, Daniel, Brender, Sydney, Song, Linghao, Huang, Ling, Zhang, Zhenyu, Steele, Nina, Regel, Ivonne, Bednar, Filip, Crawford, Howard C (December 2023) ROR2 regulates cellular plasticity in pancreatic neoplasia and adenocarcinoma. bioRxiv. (Submitted)

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DOI: 10.1101/2023.12.13.571566


Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells to precancerous lesions to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We found 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. We have identified the receptor tyrosine kinase Ror2 as marker of a gastric metaplasia (SPEM)-like identity. Ablation of Ror2 in a mouse model of pancreatic tumorigenesis promoted a switch to a gastric pit cell identity that was largely persistent upon progression to carcinoma. In both human and mouse pancreatic cancer, ROR2 activity continued to antagonize the gastric pit cell identity, strongly promoting an epithelial mesenchymal transition, conferring resistance to KRAS inhibition, and vulnerability to AKT inhibition.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders
diseases & disorders > neoplasms
diseases & disorders > cancer > cancer types > pancreatic cancer
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Preall lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 14 December 2023
Date Deposited: 16 Jan 2024 14:25
Last Modified: 16 Jan 2024 14:25
PMCID: PMC10760092
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