Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma

Item Type:	Article
Title:	Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma
Creators Name:	Kopp, J.L. and von Figura, G. and Mayes, E. and Liu, F.F. and Dubois, C.L. and Morris, J.P. and Pan, F.C. and Akiyama, H. and Wright, C.V.E. and Jensen, K. and Hebrok, M. and Sander, M.
Abstract:	Tumors are largely classified by histologic appearance, yet morphologic features do not necessarily predict cellular origin. To determine the origin of pancreatic ductal adenocarcinoma (PDA), we labeled and traced pancreatic cell populations after induction of a PDA-initiating Kras mutation. Our studies reveal that ductal and stem-like centroacinar cells are surprisingly refractory to oncogenic transformation, whereas acinar cells readily form PDA precursor lesions with ductal features. We show that formation of acinar-derived premalignant lesions depends on ectopic induction of the ductal gene Sox9. Moreover, when concomitantly expressed with oncogenic Kras, Sox9 accelerates formation of premalignant lesions. These results provide insight into the cellular origin of PDA and suggest that its precursors arise via induction of a duct-like state in acinar cells.
Keywords:	Acinar Cells, Pancreatic Ductal Carcinoma, ras Genes, Metaplasia, Mutation, Pancreatic Neoplasms, Precancerous Conditions, SOX9 Transcription Factor
Source:	Cancer Cell
ISSN:	1535-6108
Publisher:	Cell Press
Volume:	22
Number:	6
Page Range:	737-50
Date:	11 December 2012
Official Publication:	https://doi.org/10.1016/j.ccr.2012.10.025
PubMed:	View item in PubMed

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