title: HDAC2 promotes loss of primary cilia in pancreatic ductal adenocarcinoma.
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.
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan kobayt@bs.naist.jp.
authors.forename: Tetsuo
authors.identifier: 0000-0003-0698-7224
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Nakazono
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Tokuda
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mashima
authors.affiliation: Department of Pathology and Cancer Institute, Smilow Research Center, New York University School of Medicine, New York, NY, USA.
authors.forename: Brian David
authors.initials: BD
authors.lastname: Dynlacht
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: D064096:Aurora Kinase A / Q000378:metabolism; D015415:Biomarkers; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002923:Cilia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D011905:Genes, ras; D056464:Histone Deacetylase 2 / Q000235:genetics* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D056572:Histone Deacetylase Inhibitors; D064096:Aurora Kinase A; D056464:Histone Deacetylase 2
keywords: HDAC2; pancreatic ductal adenocarcinoma; primary cilia