Histone deacetylase inhibitors induce invasion of human melanoma cells in vitro via differential regulation of N-cadherin expression and RhoA activity

BMC Cancer

Research Article

Alejandro Díez-Torre¹  Ricardo Andrade¹  Olivier De Wever²  María Díaz-Núñez³  Margarita Silió³  Jon Arluzea⁴  Juan Aréchaga⁵ 

[1] Analytical & High Resolution Biomedical Microscopy Core Facility, University of the Basque Country (UPV/EHU), Leioa, Spain;Laboratory of Experimental Cancer Research, Department of Radiotherapy and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium;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;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;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;Department of Cell Biology & Histology, Faculty of Medicine & Dentistry, University of the Basque Country, E-48940, Leioa, Spain;

关键词: Histone deacetylase inhibitors;    HDACi;    Melanoma;    Cell invasion;    N-cadherin;    RhoA;   

DOI  :  10.1186/s12885-016-2693-3

 received in 2015-06-25, accepted in 2016-08-09,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundHistone 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.MethodsMatrigel 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.ResultsHDACi 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.ConclusionThese 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.

【 授权许可】

CC BY   
© The Author(s). 2016