1. Tetraspanin 8-Rictor-Integrin α3 Complex Is Required for Glioma Cell Migration
- Author
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Liuguan Bian, Qingfang Sun, Yixin Pan, Shikun Zhan, Bomin Sun, Si-Jian Pan, and Wei Liu
- Subjects
Small interfering RNA ,endocrine system ,rictor ,Integrin alpha3 ,Tetraspanins ,Integrin ,Mechanistic Target of Rapamycin Complex 2 ,AKT and cell migration ,mTORC2 ,Catalysis ,Article ,lcsh:Chemistry ,Inorganic Chemistry ,Tetraspanin ,Cell Movement ,Glioma ,Cell Line, Tumor ,medicine ,Humans ,Physical and Theoretical Chemistry ,lcsh:QH301-705.5 ,Molecular Biology ,Protein kinase B ,Spectroscopy ,PI3K/AKT/mTOR pathway ,Protein Kinase C ,Gene knockdown ,biology ,integrin α3 ,TOR Serine-Threonine Kinases ,Organic Chemistry ,General Medicine ,malignant glioma ,medicine.disease ,tetraspanin 8 ,Computer Science Applications ,Cell biology ,Rapamycin-Insensitive Companion of mTOR Protein ,lcsh:Biology (General) ,lcsh:QD1-999 ,Multiprotein Complexes ,biology.protein ,Cancer research ,Carrier Proteins ,Proto-Oncogene Proteins c-akt ,Protein Binding - 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.
- Published
- 2015