title: Geranylgeranyltransferase I regulates HIF-1α promoting glioblastoma cell migration and invasion.
abstract: Glioblastoma multiforme is a highly migratory and invasive brain tumor in which hypoxia inducible factor-1α (HIF-1α) plays important roles. However, the underlying mechanisms regulating the action of HIF-1α in glioma cell migration and invasion ability remain unclear. We reported here that HIF-1α was regulated by geranylgeranyltransferase I (GGTI), a protein prenylation transferase, and then promoted glioma cell migration and invasion. The migratory and invasive ability of glioma cells were enhanced by hypoxia treatment but inhibited by down-regulation of HIF-1α. GGTI activity inhibition or GGTI specific β subunit (GGTI β) knocking-down decreased HIF-1α protein level. In addition, down-regulation of GGTI β inhibited migration and invasion of glioma cells under hypoxia, while GGTI β over-expression promoted it. Furthermore, the effect of GGTI β over-expression on cell migration and invasion was abolished by HIF-1α down-regulation. In summary, our study showed, for the first time, that HIF-1α was regulated by protein prenylation transferase GGTI and mediated the effect of GGTI on glioma cell migration and invasion.
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou 221002, Jiangsu, People's Republic of China. xpzhou@xzmc.edu.cn
authors.forename: Xiuping
authors.initials: X
authors.lastname: Zhou
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
authors.forename: Jiantong
authors.initials: J
authors.lastname: Jiao
authors.forename: Wenbin
authors.initials: W
authors.lastname: Bian
authors.forename: Xu
authors.initials: X
authors.lastname: Song
authors.forename: Jianbing
authors.initials: J
authors.lastname: Mo
authors.forename: Ben
authors.initials: B
authors.lastname: Sang
authors.forename: Yinfu
authors.initials: Y
authors.lastname: Xu
authors.forename: Jinming
authors.initials: J
authors.lastname: Qian
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Chao
authors.forename: Rutong
authors.initials: R
authors.lastname: Yu
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering; D014162:Transfection
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I