AI Article Synopsis
- - The study discusses how pancreatic ductal adenocarcinoma (PDA) typically develops after a delay due to the activation of mutant KRAS, but introduces a new mouse model where the ataxia telangiectasia group D complementing gene (ATDC) speeds up the tumor formation process when combined with KRAS.
- - ATDC enhances the expression of CD44 in pancreatic intraepithelial neoplasia (PanIN) lesions by activating β-catenin signaling, which triggers an epithelial-to-mesenchymal transition (EMT) seen in advanced cancer cell characteristics.
- - The findings reveal that ATDC works as a key regulator in promoting the EMT process in pancreatic cancer progression, highlighting its role in
Article Abstract
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 β-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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298136 | PMC |
| http://dx.doi.org/10.1101/gad.253591.114 | DOI Listing |
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