Role of primary cilium in pancreatic ductal adenocarcinoma (Review)

Int J Oncol. 2020 Nov;57(5):1095-1102. doi: 10.3892/ijo.2020.5121. Epub 2020 Sep 14.

Abstract

The primary cilium is a non‑motile cellular structure extending from the apical membrane of epithelial cells that is involved in several processes due to its ability to receive and elaborate different signals. Ciliogenesis and its obliteration are essential for proliferating cells, and several signalling pathways are responsible for their regulation. In fact, the primary cilium is a central hub for numerous signalling pathways implicated in a variety of biological processes, such as the Hedgehog, mammalian target of rapamycin and Wnt pathways. Loss of primary cilia has been recently correlated with different types of tumours, including pancreatic ductal adenocarcinoma (PDAC). K‑Ras and HDAC2 were recently identified as possible ciliogenesis regulators in PDAC, likely acting through Aurora A kinase (AURKA) which, in turn, controls inositol polyphosphate‑5‑phosphatase E. However, the exact molecular mechanisms underlying this regulatory effect remain to be fully elucidated. In the present study, the regulation of the main genes involved in primary cilia assembly/resorption was reconstructed showing the links with the Hedgehog and phosphoinositide 3‑kinase/AKT pathways. Finally, by analysing gene expression databases, the regulatory genes that have high probability to be associated with prognosis, histological grade and pathological stage in patients with PDAC have been highlighted. However, further experimental studies are required to reach definitive conclusions on the roles of these genes. Improving our understating of ciliogenesis and its regulators may help develop ciliotherapies using histone deacetylase and AURKA inhibitors, which may induce re‑differentiation of tumour cells into normal cells by reducing tumour growth or inducing apoptosis of cancer cells.

Keywords: cilia; pancreatic neoplasms; histone deacetylase 6; histone deacetylase 2; aurora kinase.

Publication types

  • Review

MeSH terms

  • Aurora Kinase A / physiology
  • Carcinoma, Pancreatic Ductal / drug therapy
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cilia / drug effects
  • Cilia / physiology*
  • Gene Expression Regulation, Neoplastic
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • Phosphatidylinositol 3-Kinases / physiology
  • Signal Transduction

Substances

  • Histone Deacetylase Inhibitors
  • Aurora Kinase A