Methyl-CpG-binding domain 3 inhibits epithelial-mesenchymal transition in pancreatic cancer cells via TGF-β/Smad signalling

Br J Cancer. 2017 Jan 3;116(1):91-99. doi: 10.1038/bjc.2016.397. Epub 2016 Nov 29.


Background: Methyl-CpG-binding domain 3 (MBD3) is an aberrant expression in human malignancies. However, the role of MBD3 in pancreatic cancer progression remains to be clarified. In this study, we investigated the effects of MBD3 on the epithelial-mesenchymal transition (EMT), and the underlying mechanism in pancreatic cancer cells.

Methods: The abilities of migration and invasion were examined by transwell and BD Matrigel invasion assays. EMT and TGF-β/Smad signalling were evaluated.

Results: First, we find that MBD3 expression is lower in pancreatic cancer tissues than that in non-tumour tissues, and patients with lower MBD3 levels survive significantly less than those with higher levels. Subsequently, we find that MBD3 knockdown promotes the abilities of migration and invasion, while MBD3 overexpression inhibits the above abilities. Also, MBD3 knockdown remarkably increases mesenchymal markers expression of Vimentin, α-SMA, Snail, N-cadherin, β-catenin, and downregulates epithelial markers expression of E-cadherin. On the contrary, MBD3 overexpression results in the opposite effects. Further evidence reveals that MBD3 knockdown up-regulates expression of TGF-β, and then activates p-Smad2 and p-Smad3, while MBD3 overexpression results in downregulation of TGF-β, p-Smad2, and p-Smad3.

Conclusions: MBD3 inhibits EMT in pancreatic cancer cells probably via TGF-β/Smad signalling, and may be a new candidate target for diagnostics and prognosis of pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • DNA-Binding Proteins / physiology*
  • Epithelial-Mesenchymal Transition / genetics*
  • HEK293 Cells
  • Humans
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • Signal Transduction / genetics
  • Smad Proteins / metabolism*
  • Transforming Growth Factor beta / metabolism*


  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • MBD3 protein, human
  • Smad Proteins
  • Transforming Growth Factor beta