Student and Faculty Publications
Publication Date
8-4-2023
Journal
Cancer Discovery
Abstract
Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas are bona fide precursor lesions of pancreatic ductal adenocarcinoma (PDAC). The most common subtype of IPMNs harbor a gastric foveolar-type epithelium, and these low-grade mucinous neoplasms are harbingers of IPMNs with high-grade dysplasia and cancer. The molecular underpinning of gastric differentiation in IPMNs is unknown, although identifying drivers of this indolent phenotype might enable opportunities for intercepting progression to high-grade IPMN and cancer. We conducted spatial transcriptomics on a cohort of IPMNs, followed by orthogonal and cross species validation studies, which established the transcription factor NKX6-2 as a key determinant of gastric cell identity in low-grade IPMNs. Loss of NKX6-2 expression is a consistent feature of IPMN progression, while re-expression of NKX6-2 in murine IPMN lines recapitulates the aforementioned gastric transcriptional program and glandular morphology. Our study identifies NKX6-2 as a previously unknown transcription factor driving indolent gastric differentiation in IPMN pathogenesis.
Keywords
Animals, Mice, Carcinoma, Pancreatic Ductal, Cell Differentiation, Neoplasms, Cystic, Mucinous, and Serous, Pancreas, Pancreatic Intraductal Neoplasms, Pancreatic Neoplasms, Transcriptome, Tumor Microenvironment
Included in
Bioinformatics Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Digestive System Diseases Commons, Medical Microbiology Commons, Neoplasms Commons, Oncology Commons
Comments
Supplementary Materials
PMID: 37285225