Loss of ATM accelerates pancreatic cancer formation and epithelial-mesenchymal transition
2015 | journal article. A publication with affiliation to the University of Göttingen.
Jump to: Cite & Linked | Documents & Media | Details | Version history
Documents & Media
Details
- Authors
- Russell, Ronan; Perkhofer, Lukas; Liebau, Stefan; Lin, Qiong; Lechel, Andre; Feld, Fenja M.; Hessmann, Elisabeth ; Gaedcke, Jochen; Guethle, Melanie; Zenke, Martin; Hartmann, Daniel; von Figura, Guido; Weissinger, Stephanie E.; Rudolph, K. Lenhard; Moeller, Peter; Lennerz, Jochen K.; Seufferlein, Thomas; Wagner, Martin; Kleger, Alexander
- Abstract
- Pancreatic ductal adenocarcinoma (PDAC) is associated with accumulation of particular oncogenic mutations and recent genetic sequencing studies have identified ataxia telangiectasia-mutated (ATM) mutations in PDAC cohorts. Here we report that conditional deletion of ATM in a mouse model of PDAC induces a greater number of proliferative precursor lesions coupled with a pronounced fibrotic reaction. ATM-targeted mice display altered TGF beta-superfamily signalling and enhanced epithelial-to-mesenchymal transition (EMT) coupled with shortened survival. Notably, our mouse model recapitulates many features of more aggressive human PDAC subtypes. Particularly, we report that low expression of ATM predicts EMT, a gene signature specific for Bmp4 signalling and poor prognosis in human PDAC. Our data suggest an intimate link between ATM expression and pancreatic cancer progression in mice and men.
- Issue Date
- 2015
- Status
- published
- Publisher
- Nature Publishing Group
- Journal
- Nature Communications
- ISSN
- 2041-1723