| First Author | Wang L | Year | 2015 |
| Journal | Genes Dev | Volume | 29 |
| Issue | 2 | Pages | 171-83 |
| PubMed ID | 25593307 | Mgi Jnum | J:218233 |
| Mgi Id | MGI:5617063 | Doi | 10.1101/gad.253591.114 |
| Citation | Wang L, et al. (2015) ATDC induces an invasive switch in KRAS-induced pancreatic tumorigenesis. Genes Dev 29(2):171-83 |
| abstractText | The initiation of pancreatic ductal adenocarcinoma (PDA) is linked to activating mutations in KRAS. However, in PDA mouse models, expression of oncogenic mutant KRAS during development gives rise to tumors only after a prolonged latency or following induction of pancreatitis. Here we describe a novel mouse model expressing ataxia telangiectasia group D complementing gene (ATDC, also known as TRIM29 [tripartite motif 29]) that, in the presence of oncogenic KRAS, accelerates pancreatic intraepithelial neoplasia (PanIN) formation and the development of invasive and metastatic cancers. We found that ATDC up-regulates CD44 in mouse and human PanIN lesions via activation of beta-catenin signaling, leading to the induction of an epithelial-to-mesenchymal transition (EMT) phenotype characterized by expression of Zeb1 and Snail1. We show that ATDC is up-regulated by oncogenic Kras in a subset of PanIN cells that are capable of invading the surrounding stroma. These results delineate a novel molecular pathway for EMT in pancreatic tumorigenesis, showing that ATDC is a proximal regulator of EMT. |
