title: GOLPH3 promotes glioblastoma cell migration and invasion via the mTOR-YB1 pathway in vitro.
abstract: The identification of genes involved in carcinogenesis and tumor progression is of great interest, since these genes might be possible as candidates for new tumor targeted therapy strategies. Our previous study shows that Golgi phosphoprotein 3 (GOLPH3) is involved in glioma cell migration and invasion, the critical characteristics of malignant gliomas. In this study, we explored the mechanism of GOLPH3 affecting cell migration and invasion and found that GOLPH3 promotes glioblastoma (GBM) cell migration and invasion via the mammalian target of rapamycin(mTOR)-Y-box binding protein-1 (YB1) pathway in vitro. Both the protein levels of GOLPH3 and YB1 were up-regulated in human glioma tissues and they exhibited direct correlation with each other. In addition, down-regulation of GOLPH3 inhibited glioma cell migration and invasion, while over-expression of GOLPH3 enhanced them. Meanwhile, GOLPH3 down-regulation led to a significant decrease of YB1 level as well as mTOR activity, both required for glioma cell migration and invasion. On the contrary, YB1 level and mTOR activity increased after GOLPH3 over-expression. YB1 down-regulation or mTOR ATP site inhibitor INK128 treatment inhibited cell migration and invasion, similar to the effect of GOLPH3 down-regulation. Furthermore, over-expression of GOLPH3 induced glioma cell migration and invasion was blocked by INK128 and YB1 down-regulation. Taken together, these results show that GOLPH3 promotes glioblastoma cell migration and invasion via the mTOR-YB1pathway, indicating that GOLPH3-mTOR-YB1 pathway might be a new therapeutic target for glioma treatment.
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Ding
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Jianbing
authors.initials: J
authors.lastname: Mo
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Ben
authors.initials: B
authors.lastname: Sang
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Jinxia
authors.initials: J
authors.lastname: Hu
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Shao
authors.initials: S
authors.lastname: Xie
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Zhan
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Lu
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Minglin
authors.initials: M
authors.lastname: Yang
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Bian
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Rutong
authors.initials: R
authors.lastname: Yu
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D051840:Y-Box-Binding Protein 1 / Q000235:genetics*
chemical_list: C429024:GOLPH3 protein, human; D008565:Membrane Proteins; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: GOLPH3; YB1; glioma; invasion; mTOR; migration