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

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 fo...

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Autores principales: Pan, Si-Jian, Zhan, Shi-Kun, Pan, Yi-Xin, Liu, Wei, Bian, Liu-Guan, Sun, Bomin, Sun, Qing-Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394480/
https://www.ncbi.nlm.nih.gov/pubmed/25761241
http://dx.doi.org/10.3390/ijms16035363
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author Pan, Si-Jian
Zhan, Shi-Kun
Pan, Yi-Xin
Liu, Wei
Bian, Liu-Guan
Sun, Bomin
Sun, Qing-Fang
author_facet Pan, Si-Jian
Zhan, Shi-Kun
Pan, Yi-Xin
Liu, Wei
Bian, Liu-Guan
Sun, Bomin
Sun, Qing-Fang
author_sort Pan, Si-Jian
collection PubMed
description 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.
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spelling pubmed-43944802015-05-21 Tetraspanin 8-Rictor-Integrin α3 Complex Is Required for Glioma Cell Migration Pan, Si-Jian Zhan, Shi-Kun Pan, Yi-Xin Liu, Wei Bian, Liu-Guan Sun, Bomin Sun, Qing-Fang Int J Mol Sci Article 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. MDPI 2015-03-09 /pmc/articles/PMC4394480/ /pubmed/25761241 http://dx.doi.org/10.3390/ijms16035363 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pan, Si-Jian
Zhan, Shi-Kun
Pan, Yi-Xin
Liu, Wei
Bian, Liu-Guan
Sun, Bomin
Sun, Qing-Fang
Tetraspanin 8-Rictor-Integrin α3 Complex Is Required for Glioma Cell Migration
title Tetraspanin 8-Rictor-Integrin α3 Complex Is Required for Glioma Cell Migration
title_full Tetraspanin 8-Rictor-Integrin α3 Complex Is Required for Glioma Cell Migration
title_fullStr Tetraspanin 8-Rictor-Integrin α3 Complex Is Required for Glioma Cell Migration
title_full_unstemmed Tetraspanin 8-Rictor-Integrin α3 Complex Is Required for Glioma Cell Migration
title_short Tetraspanin 8-Rictor-Integrin α3 Complex Is Required for Glioma Cell Migration
title_sort tetraspanin 8-rictor-integrin α3 complex is required for glioma cell migration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394480/
https://www.ncbi.nlm.nih.gov/pubmed/25761241
http://dx.doi.org/10.3390/ijms16035363
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