title: Histone deacetylase 6 promotes growth of glioblastoma through inhibition of SMAD2 signaling.
abstract: Histone deacetylases (HDACs) play a role in the tumorigenesis of glioblastoma multiforme (GBM), whereas the underlying mechanism has not been elucidated. Here, we reported significantly higher HDAC6 levels in GBM from the patients. GBM cell growth was significantly inhibited by ACY-1215, a specific HDAC6 inhibitor. Further analyses show that HDAC6 may promote growth of GBM cells through inhibition of SMAD2 phosphorylation to downregulate p21. Thus, our data demonstrate a previously unrecognized regulation pathway in that HDAC6 increases GBM growth through attenuating transforming growth factor β (TGFβ) receptor signaling.
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, 510282, China.|Department of Neurosurgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, 510282, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Jinan University, 613 West Huangpu Road, Guangzhou, 510630, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, 510282, China. xiangyu_wang14@163.com.|Department of Neurosurgery, The First Affiliated Hospital of Jinan University, 613 West Huangpu Road, Guangzhou, 510630, China. xiangyu_wang14@163.com.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Wang
mesh_terms: D000107:Acetylation; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage; D006655:Histone Deacetylases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D011743:Pyrimidines / Q000008:administration & dosage; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000096:biosynthesis* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D054462:p21-Activated Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011743:Pyrimidines; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; C515907:PAK2 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; C572255:ricolinostat
keywords: GBM; HDACs; SMAD2; p21