N-cadherin functions as a growth suppressor in a model of K-ras-induced PanIN

Y. Su, J. Li, C. Shi, R. H. Hruban, G. L. Radice

Research output: Contribution to journalArticlepeer-review

Abstract

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-rasG12D 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-rasG12D mice. Decreased E-cadherin and redistribution of β-catenin accompanied the loss of N-cadherin in pancreatic ductal epithelial cells (PDEC). Nuclear accumulation of β-catenin and its transcription co-activator Tcf4 led to activation of Wnt/β-catenin target genes. Unexpectedly, loss of N-cadherin in the K-rasG12D 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.

Original languageEnglish (US)
Pages (from-to)3335-3341
Number of pages7
JournalOncogene
Volume35
Issue number25
DOIs
StatePublished - Jun 23 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'N-cadherin functions as a growth suppressor in a model of K-ras-induced PanIN'. Together they form a unique fingerprint.

Cite this