title: Tetraspanin 8-rictor-integrin α3 complex is required for glioma cell migration.
abstract: The malignant glioma remains one of the most aggressive human malignancies with extremely poor prognosis. Glioma cell invasion and migration are the main causes of death. In the current study, we studied the expression and the potential functions of tetraspanin 8 (Tspan8) in malignant gliomas. We found that Tspan8 expression level is high in both malignant glioma tissues and in several human glioma cell lines, where it formed a complex integrin α3 and rictor, the latter is a key component of mammalian target of rapamycin (mTOR) complex 2 (mTORC2). Disruption of this complex, through siRNA-mediated knockdown of anyone of these three proteins, inhibited U251MG glioma cell migration in vitro. We further showed that Tspan8-rictor association appeared required for mTORC2 activation. Knockdown of Tspan8 by the targeted siRNAs prevented mTOR-rictor (mTORC2) assembly as well as phosphorylation of AKT (Ser-473) and protein kinase C α (PKCα) in U251MG cells. Together, these results demonstrate that over-expressed Tspan8 in malignant glioma forms a complex with rictor and integrin α3 to mediate mTORC2 activation and glioma cell migration. Therefore, targeting Tspan8-rictor-integrin α3 complex may provide a potential therapeutic intervention for malignant glioma.
authors.affiliation: Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Shanghai Ruijin Second Road, Shanghai 200025, China. pansijian163@163.com.
authors.forename: Si-Jian
authors.initials: SJ
authors.lastname: Pan
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Shanghai Ruijin Second Road, Shanghai 200025, China. shikun_zhan@163.com.
authors.forename: Shi-Kun
authors.initials: SK
authors.lastname: Zhan
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Shanghai Ruijin Second Road, Shanghai 200025, China. yixinpan@163.com.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Pan
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Shanghai Ruijin Second Road, Shanghai 200025, China. doctorliuwei@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Shanghai Ruijin Second Road, Shanghai 200025, China. blg11118@rjh.com.cn.
authors.forename: Liu-Guan
authors.initials: LG
authors.lastname: Bian
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Shanghai Ruijin Second Road, Shanghai 200025, China. bomin_sun@163.com.
authors.forename: Bomin
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Shanghai Ruijin Second Road, Shanghai 200025, China. sunqingfang11@163.com.
authors.forename: Qing-Fang
authors.initials: QF
authors.lastname: Sun
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D039422:Integrin alpha3 / Q000235:genetics / Q000378:metabolism*; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D059470:Tetraspanins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D039422:Integrin alpha3; D046912:Multiprotein Complexes; C492571:RICTOR protein, human; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; C065609:TSPAN8 protein, human; D059470:Tetraspanins; D000076225:Mechanistic Target of Rapamycin Complex 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D011493:Protein Kinase C