title: HDAC6 regulates neuroblastoma cell migration and may play a role in the invasion process.
abstract: Neuroblastoma is one of the most prevalent pediatric extracranial solid tumors and is often diagnosed after dissemination has occurred. Despite recent advances in multimodal therapies of this malignancy, its therapeutic efficacy remains poor. Novel treatment strategies are thus in great need. Herein, we demonstrate that histone deacetylase 6 (HDAC6), a member of the deacetylase family that is localized predominantly in the cytoplasm, is involved in neuroblastoma dissemination. HDAC6 expression in neuroblastoma tissue samples varied with the site of the tumor. HDAC6 showed little impact on the proliferation of neuroblastoma cells. Instead, downregulation of HDAC6 expression by RNA interference or inhibition of its catalytic activity by the pharmacological inhibitor tubacin significantly decreased the migration of 3 human malignant neuroblastoma cell lines and reduced the invasion ability of one of the 3 cell lines, but only slightly affected the migration and invasion of human normal brain glial cells. Our data further revealed that the regulation of neuroblastoma cell migration by HDAC6 was mediated by its effects on cell polarization and adhesion. These findings suggest a role for HDAC6 in neuroblastoma dissemination and a potential of using HDAC6 inhibitors for the treatment of this malignancy.
authors.affiliation: a State Key Laboratory of Medicinal Chemical Biology; College of Life Sciences ; Nankai University ; Tianjin China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhang
authors.forename: Ningning
authors.initials: N
authors.lastname: Liu
authors.forename: Songbo
authors.initials: S
authors.lastname: Xie
authors.forename: Xianfei
authors.initials: X
authors.lastname: He
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Dengwen
authors.initials: D
authors.lastname: Li
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D004789:Enzyme Activation; D015870:Gene Expression; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases
keywords: DAPI, 4′, 6-diamidino-2-phenylindole; HDAC6; HDAC6, histone deacetylase 6; MTT, 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide; SRB, sulforhodamine B; adhesion; calcein-AM, calcein-acetoxymethyl; cell invasion; cell migration; dissemination; neuroblastoma; polarization