Both HDAC5 and HDAC6 are required for the proliferation and metastasis of melanoma cells

Abstract

BackgroundHistone deacetylase (HDAC) inhibitors are widely used in clinical investigation as novel drug targets. For example, panobinostat and vorinostat have been used to treat patients with melanoma. However, HDAC inhibitors are small-molecule compounds without a specific target, and their mechanism of action is unclear. Therefore, it is necessary to investigate which HDACs are required for the proliferation and metastasis of melanoma cells.MethodsWe used overexpression and knocking down lentivirus to clarify the influence of HDAC5 and HDAC6 in melanoma development. Also, we introduced stable HDAC5 or HDAC6 knockdown cells into null mice and found that the knockdown cells were unable to form solid tumors. Finally, we tested HDAC5 and HDAC6 expression and sub-location in clinical melanoma tissues and tumor adjacent tissues.ResultsIn this study, and found that HDAC5 and HDAC6 were highly expressed in melanoma cells but exhibited low expression levels in normal skin cells. Furthermore, we knocked down HDAC5 or HDAC6 in A375 cells and demonstrated that both HDAC5 and HDAC6 contributed to the proliferation and metastasis of melanoma cells.ConclusionsThis study demonstrated both HDAC5 and HDAC6 were required for melanoma cell proliferation and metastasis through different signaling pathways.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0753-0) contains supplementary material, which is available to authorized users.

The HDAC inhibitor AR42 interacts with pazopanib to kill trametinib/dabrafenib-resistant melanoma cells in vitro and in vivo

“…Knock down of HDAC6 combined with knock down of HDAC2 or of HDAC10 caused a significant high level of killing when combined with pazopanib (Figure 7A, lower). The HSP90-associated HDAC, HDAC6, has been proposed to regulate autophagic flux, with protein acetylation reducing the maturation of autophagosomes into autolysosomes [27–30]. To test for a role of HDAC6 in our system, we over-expressed HDAC6, either using a catalytically active wild type protein or a protein that lacks activity in the two deacetylase catalytic activity sites.…”

Andrographolide inhibits proliferation and induces cell cycle arrest and apoptosis in human melanoma cells

“…Melanoma is a malignant tumor of melanocytes and is considered to be the most invasive and dangerous cutaneous cancer (1). The median 5-year survival rate is <5% following metastasis and the incidence of melanoma has increased over the past few decades (2).…”

The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair

“…Apart from the role of SIRT1 in NER, the overexpressed HDACs in melanoma cells (16,26) (Table 1) seem to also play a role in stimulating NER, as HDAC inhibition by sodium butyrate, an inhibitor of class I and class IIA HDACs (84), inhibits removal of bulky lesions by NER in these cells (38). Contrary to melanoma cells, HDAC inhibition with sodium butyrate in normal human fibroblasts enhances NER upon UV irradiation (85).…”

“…Overexpressed HDAC6 in melanoma cancers (26) could, therefore, contribute to the resistance of this cancer to methylating agent based therapies with dacarbazine and temozolomide as these chemotherapeutics require an intact MMR system to kill cells (193). …”