title: Histone deacetylase inhibition modulates E-cadherin expression and suppresses migration and invasion of anaplastic thyroid cancer cells.
abstract: BACKGROUND
  Anaplastic thyroid cancer cells are characterized by a mesenchymal phenotype, as revealed by spindle-shaped cells and absent or reduced levels of E-cadherin. Epigenetic silencing is considered one of the leading mechanisms of E-cadherin impairment, which causes the acquisition of the invasive and metastatic phenotype of anaplastic thyroid cancer.
  
  
  OBJECTIVE
  In this study we investigated the effects of histone deacetylase inhibition on E-cadherin expression, cell motility, and invasion in anaplastic thyroid cancer cell cultures.
  
  
  METHODS
  Three stabilized cell lines and primary cultures of anaplastic thyroid cancer were treated with various histone deacetylase inhibitors. After treatment, we evaluated histone acetylation by Western blotting and E-cadherin expression by RT-real time PCR. The proper localization of E-cadherin/β-catenin complex was assessed by immunofluorescence and Western blot. Transcription activity of β-catenin was measured by luciferase reporter gene and cyclin D1 expression. The effect on cell motility and invasion was studied both in vitro using scratch-wound and transwell invasion assays and in anaplastic thyroid carcinomas tumor xenografts in mice in vivo.
  
  
  RESULTS
  Histone deacetylase inhibition induced the E-cadherin expression and the proper membrane localization of the E-cadherin/β-catenin complex, leading to reduced cancer cell migration and invasion.
  
  
  CONCLUSIONS
  We here demonstrate an additional molecular mechanism for the anticancer effect of histone deacetylase inhibition. The antiinvasive effect in addition to the cytotoxic activity of histone deacetylase inhibitors opens up therapeutic perspectives for the anaplastic thyroid tumor that does not respond to conventional therapy.
authors.affiliation: Department of Clinical Pathophysiology, University of Turin, 10126 Torino, Italy.
authors.forename: Maria Graziella
authors.initials: MG
authors.lastname: Catalano
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Fortunati
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Pugliese
authors.forename: Francesca
authors.initials: F
authors.lastname: Marano
authors.forename: Loredana
authors.initials: L
authors.lastname: Ortoleva
authors.forename: Roberta
authors.initials: R
authors.lastname: Poli
authors.forename: Sofia
authors.initials: S
authors.lastname: Asioli
authors.forename: Andrea
authors.initials: A
authors.lastname: Bandino
authors.forename: Nicola
authors.initials: N
authors.lastname: Palestini
authors.forename: Cristina
authors.initials: C
authors.lastname: Grange
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bussolati
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Boccuzzi
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology; D007211:Indoles; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D000077767:Panobinostat; D021381:Protein Transport / Q000187:drug effects; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism
chemical_list: D001549:Benzamides; D015820:Cadherins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D011725:Pyridines; D051176:beta Catenin; C118739:entinostat; C012589:trichostatin A; D000077767:Panobinostat