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| Content Provider | PubMed Central |
|---|---|
| Author | Pan, Si-jian Zhan, Shi-kun Pan, Yi-xin Liu, Wei Bian, Liu-guan Sun, Bomin Sun, Qing-fang |
| Editor | Cho, William Chi-shing |
| Copyright Year | 2015 |
| 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. |
| Related Links | http://dx.doi.org/10.3390/ijms16035363 |
| Ending Page | 5374 |
| Page Count | 12 |
| Starting Page | 5363 |
| File Format | |
| ISSN | 14220067 |
| e-ISSN | 14220067 |
| Journal | International Journal of Molecular Sciences |
| Issue Number | 3 |
| Volume Number | 16 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2015-03-01 |
| Access Restriction | Open |
| Rights Holder | MDPI |
| Subject Keyword | Physical and Theoretical Chemistry Inorganic Chemistry Organic Chemistry Spectroscopy Molecular Biology Catalysis Computer Science Applications Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Spectroscopy Organic Chemistry Medicine Molecular Biology Physical and Theoretical Chemistry Catalysis Inorganic Chemistry Computer Science Applications |
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