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

(2016) BMC CANCER. 16(1).
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Abstract
Background: 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. Methods: 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. Results: 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. Conclusion: 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.
Keywords
Histone deacetylase inhibitors, HDACi, Melanoma, Cell invasion, N-cadherin, RhoA, EPITHELIAL-MESENCHYMAL TRANSITIONS, CANCER-CELLS, BREAST-CANCER, CARCINOMA METASTASIS, PANCREATIC-CANCER, GENE-EXPRESSION, HDAC INHIBITORS, VALPROIC ACID, LUNG-CANCER, STEM-CELLS

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Chicago
Díaz-Núñez, María, Alejandro Díez-Torre, Olivier De Wever, Ricardo Andrade, Jon Arluzea, Margarita Silió, and Juan Aréchaga. 2016. “Histone Deacetylase Inhibitors Induce Invasion of Human Melanoma Cells in Vitro via Differential Regulation of N-cadherin Expression and RhoA Activity.” Bmc Cancer 16 (1).
APA
Díaz-Núñez, M., Díez-Torre, A., De Wever, O., Andrade, R., Arluzea, J., Silió, M., & Aréchaga, J. (2016). Histone deacetylase inhibitors induce invasion of human melanoma cells in vitro via differential regulation of N-cadherin expression and RhoA activity. BMC CANCER, 16(1).
Vancouver
1.
Díaz-Núñez M, Díez-Torre A, De Wever O, Andrade R, Arluzea J, Silió M, et al. Histone deacetylase inhibitors induce invasion of human melanoma cells in vitro via differential regulation of N-cadherin expression and RhoA activity. BMC CANCER. 2016;16(1).
MLA
Díaz-Núñez, María et al. “Histone Deacetylase Inhibitors Induce Invasion of Human Melanoma Cells in Vitro via Differential Regulation of N-cadherin Expression and RhoA Activity.” BMC CANCER 16.1 (2016): n. pag. Print.
@article{8515602,
  abstract     = {Background: 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. 
Methods: 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. 
Results: 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. 
Conclusion: 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.},
  articleno    = {667},
  author       = {D{\'i}az-N{\'u}{\~n}ez, Mar{\'i}a and D{\'i}ez-Torre, Alejandro and De Wever, Olivier and Andrade, Ricardo and Arluzea, Jon and Sili{\'o}, Margarita and Ar{\'e}chaga, Juan},
  issn         = {1471-2407},
  journal      = {BMC CANCER},
  language     = {eng},
  number       = {1},
  pages        = {12},
  title        = {Histone deacetylase inhibitors induce invasion of human melanoma cells in vitro via differential regulation of N-cadherin expression and RhoA activity},
  url          = {http://dx.doi.org/10.1186/s12885-016-2693-3},
  volume       = {16},
  year         = {2016},
}

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