title: Both HDAC5 and HDAC6 are required for the proliferation and metastasis of melanoma cells.
abstract: BACKGROUND
  Histone 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  This study demonstrated both HDAC5 and HDAC6 were required for melanoma cell proliferation and metastasis through different signaling pathways.
authors.affiliation: Department of Plastic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. liujiaqi1213@yahoo.com.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Plastic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. gu.jianying@zs-hospital.sh.cn.
authors.forename: Jianying
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Plastic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. feng.zihao@zs-hospital.sh.cn.
authors.forename: Zihao
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Rd, Shanghai, 201203, China. shouhunv@hotmail.com.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Huashan Hospital, Fudan University, 12 Middle Urumqi Rd, Shanghai, 200040, China. drnwzhu@126.com.
authors.forename: Ningwen
authors.initials: N
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Rd, Shanghai, 201203, China. wylu@shmu.edu.cn.
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Plastic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. qi.fazhi@zs-hospital.sh.cn.
authors.forename: Fazhi
authors.initials: F
authors.lastname: Qi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D055785:Gene Knockdown Techniques; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology*; D015854:Up-Regulation
chemical_list: C404500:HDAC5 protein, human; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases