HDAC2 promotes loss of primary cilia in pancreatic ductal adenocarcinoma

EMBO Rep. 2017 Feb;18(2):334-343. doi: 10.15252/embr.201541922. Epub 2016 Dec 27.

Abstract

Loss of primary cilia is frequently observed in tumor cells, including pancreatic ductal adenocarcinoma (PDAC) cells, suggesting that the absence of this organelle may promote tumorigenesis through aberrant signal transduction and the inability to exit the cell cycle. However, the molecular mechanisms that explain how PDAC cells lose primary cilia are still ambiguous. In this study, we found that inhibition or silencing of histone deacetylase 2 (HDAC2) restores primary cilia formation in PDAC cells. Inactivation of HDAC2 results in decreased Aurora A expression, which promotes disassembly of primary cilia. We further showed that HDAC2 controls ciliogenesis independently of Kras, which facilitates Aurora A expression. These studies suggest that HDAC2 is a novel regulator of primary cilium formation in PDAC cells.

Keywords: HDAC2; pancreatic ductal adenocarcinoma; primary cilia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aurora Kinase A / metabolism
  • Biomarkers
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cilia / drug effects
  • Cilia / metabolism*
  • Cilia / pathology*
  • Genes, ras
  • Histone Deacetylase 2 / genetics*
  • Histone Deacetylase 2 / metabolism
  • Histone Deacetylase Inhibitors / pharmacology
  • Humans
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology*
  • Signal Transduction

Substances

  • Biomarkers
  • Histone Deacetylase Inhibitors
  • Aurora Kinase A
  • Histone Deacetylase 2