title: Histone deacetylase inhibitors induce invasion of human melanoma cells in vitro via differential regulation of N-cadherin expression and RhoA activity.
abstract: Histone deacetylase inhibitors (HDACi) exert multiple cytotoxic actions on cancer cells. Currently, different synthetic HDACi are in clinical use or clinical trials; nevertheless, since both pro-invasive and anti-invasive activities have been described, there is some controversy about the effect of HDACi on melanoma cells.
  
  
  
  Matrigel and Collagen invasion assays were performed to evaluate the effect of several HDACi (Butyrate, Trichostatin A, Valproic acid and Vorinostat) on two human melanoma cell line invasion (A375 and HT-144). The expression of N- and E-Cadherin and the activity of the RhoA GTPase were analyzed to elucidate the mechanisms involved in the HDACi activity.
  
  
  
  HDACi showed a pro-invasive effect on melanoma cells in vitro. This effect was accompanied by an up-regulation of N-cadherin expression and an inhibition of RhoA activity. Moreover, the down-regulation of N-cadherin through blocking antibodies or siRNA abrogated the pro-invasive effect of the HDACi and, additionally, the inhibition of the Rho/ROCK pathway led to an increase of melanoma cell invasion similar to that observed with the HDACi treatments.
  
  
  
  These results suggest a role of N-cadherin and RhoA in HDACi induced invasion and call into question the suitability of some HDACi as antitumor agents for melanoma patients.
authors.affiliation: Laboratory of Stem Cells, Development & Cancer, Department of Cell Biology & Histology, Faculty of Medicine & Nursing, University of the Basque Country (UPV/EHU), Leioa, Biscay, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Díaz-Núñez
authors.affiliation: Analytical & High Resolution Biomedical Microscopy Core Facility, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Díez-Torre
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiotherapy and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: De Wever
authors.affiliation: Analytical & High Resolution Biomedical Microscopy Core Facility, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Andrade
authors.affiliation: Laboratory of Stem Cells, Development & Cancer, Department of Cell Biology & Histology, Faculty of Medicine & Nursing, University of the Basque Country (UPV/EHU), Leioa, Biscay, Spain.|Analytical & High Resolution Biomedical Microscopy Core Facility, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Jon
authors.initials: J
authors.lastname: Arluzea
authors.affiliation: Laboratory of Stem Cells, Development & Cancer, Department of Cell Biology & Histology, Faculty of Medicine & Nursing, University of the Basque Country (UPV/EHU), Leioa, Biscay, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Silió
authors.affiliation: Laboratory of Stem Cells, Development & Cancer, Department of Cell Biology & Histology, Faculty of Medicine & Nursing, University of the Basque Country (UPV/EHU), Leioa, Biscay, Spain. juan.arechaga@ehu.eus.|Analytical & High Resolution Biomedical Microscopy Core Facility, University of the Basque Country (UPV/EHU), Leioa, Spain. juan.arechaga@ehu.eus.|Department of Cell Biology & Histology, Faculty of Medicine & Dentistry, University of the Basque Country, E-48940, Leioa, Spain. juan.arechaga@ehu.eus.
authors.forename: Juan
authors.initials: J
authors.lastname: Aréchaga
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008545:Melanoma / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014635:Valproic Acid / Q000494:pharmacology; D000077337:Vorinostat; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002087:Butyrates; D015820:Cadherins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D034741:RNA, Small Interfering; C066737:RHOA protein, human; C012589:trichostatin A; D000077337:Vorinostat; D014635:Valproic Acid; D020742:rhoA GTP-Binding Protein
keywords: Cell invasion; HDACi; Histone deacetylase inhibitors; Melanoma; N-cadherin; RhoA