| First Author | Su Y | Year | 2016 |
| Journal | Oncogene | Volume | 35 |
| Issue | 25 | Pages | 3335-41 |
| PubMed ID | 26477318 | Mgi Jnum | J:226086 |
| Mgi Id | MGI:5695776 | Doi | 10.1038/onc.2015.382 |
| Citation | Su Y, et al. (2016) N-cadherin functions as a growth suppressor in a model of K-ras-induced PanIN. Oncogene 35(25):3335-41 |
| abstractText | Cadherin subtype switching from E-cadherin to N-cadherin is associated with the epithelial-to-mesenchymal transition (EMT), a process required for invasion and dissemination of carcinoma cells. We found that N-cadherin is expressed in human and mouse pancreatic intraepithelial neoplasia (PanIN), suggesting that N-cadherin may also have a role in early-stage pancreatic cancer. To investigate the role of N-cadherin in mouse PanIN (mPanIN), we simultaneously activated oncogenic K-ras(G12D) and deleted the N-cadherin (Cdh2) gene in the murine pancreas. Genetic ablation of N-cadherin (N-cad KO) caused hyperproliferation, accelerated mPanIN progression, and early tumor development in K-ras(G12D) mice. Decreased E-cadherin and redistribution of beta-catenin accompanied the loss of N-cadherin in pancreatic ductal epithelial cells (PDEC). Nuclear accumulation of beta-catenin and its transcription co-activator Tcf4 led to activation of Wnt/beta-catenin target genes. Unexpectedly, loss of N-cadherin in the K-ras(G12D) model resulted in increased mPanIN progression and tumor incidence. These in vivo results demonstrate for the first time that N-cadherin functions as a growth suppressor in the context of oncogenic K-ras. |
