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Int. J. Mol. Sci. 2015, 16(3), 5363-5374; doi:10.3390/ijms16035363

Tetraspanin 8-Rictor-Integrin α3 Complex Is Required for Glioma Cell Migration

1
Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Shanghai Ruijin Second Road, Shanghai 200025, China
2
Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Shanghai Ruijin Second Road, Shanghai 200025, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 5 January 2015 / Revised: 3 February 2015 / Accepted: 9 February 2015 / Published: 9 March 2015
(This article belongs to the Collection Advances in Molecular Oncology)
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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. View Full-Text
Keywords: malignant glioma; tetraspanin 8; integrin α3; rictor; mTORC2; AKT and cell migration malignant glioma; tetraspanin 8; integrin α3; rictor; mTORC2; AKT and cell migration
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Pan, S.-J.; Zhan, S.-K.; Pan, Y.-X.; Liu, W.; Bian, L.-G.; Sun, B.; Sun, Q.-F. Tetraspanin 8-Rictor-Integrin α3 Complex Is Required for Glioma Cell Migration. Int. J. Mol. Sci. 2015, 16, 5363-5374.

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