Int6/eIF3e Is Essential for Proliferation and Survival of Human Glioblastoma Cells
| Autor: | Stefania Millevoi, Christine Toulas, Nicolas Skuli, Bertand Elefterion, Elizabeth Cohen-Jonathan Moyal, Anne Cammas, Julie Sesen, Lijoy K. Mathew, Anthony Lemarié, Sarah J. Scotland, Cathy Seva |
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| Přispěvatelé: | Equipe 11-E.Moyal/C.Toulas, Abramson Family Cancer Research Institute, University of Pennsylvania, Institut Claudius Regaud, Ligue contre le cancer, Cancéropôle Grand Sud-Ouest, ARC, Sesen, Julie, University of Pennsylvania [Philadelphia] |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cell cycle checkpoint
Eukaryotic Initiation Factor-3 proliferation HIF-1α [SDV.CAN]Life Sciences [q-bio]/Cancer Biology Models Biological Article Catalysis lcsh:Chemistry Inorganic Chemistry [SDV.CAN] Life Sciences [q-bio]/Cancer RNA interference Cell Line Tumor Eukaryotic initiation factor Glioma glioma Hypoxia Inducible Factors medicine Humans Gene silencing Gene Silencing Physical and Theoretical Chemistry lcsh:QH301-705.5 Molecular Biology Spectroscopy Cell Proliferation Brain Neoplasms Cell growth Int6 Organic Chemistry glioblastoma apoptosis HIF-2α Cell Cycle Checkpoints General Medicine Cell cycle Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Computer Science Applications Cell biology Gene Expression Regulation Neoplastic lcsh:Biology (General) lcsh:QD1-999 Hypoxia-inducible factors eukaryotic translation initiation factor eIF3e RNA Interference |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, 2014, 15 (2), pp.2172-90. ⟨10.3390/ijms15022172⟩ International Journal of Molecular Sciences; Volume 15; Issue 2; Pages: 2172-2190 International Journal of Molecular Sciences, MDPI, 2014, 15 (2), pp.2172-90. ⟨10.3390/ijms15022172⟩ International Journal of Molecular Sciences, Vol 15, Iss 2, Pp 2172-2190 (2014) |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | International audience; Glioblastomas (GBM) are very aggressive and malignant brain tumors, with frequent relapses despite an appropriate treatment combining surgery, chemotherapy and radiotherapy. In GBM, hypoxia is a characteristic feature and activation of Hypoxia Inducible Factors (HIF-1α and HIF-2α) has been associated with resistance to anti-cancer therapeutics. Int6, also named eIF3e, is the "e" subunit of the translation initiation factor eIF3, and was identified as novel regulator of HIF-2α. Eukaryotic initiation factors (eIFs) are key factors regulating total protein synthesis, which controls cell growth, size and proliferation. The functional significance of Int6 and the effect of Int6/EIF3E gene silencing on human brain GBM has not yet been described and its role on the HIFs is unknown in glioma cells. In the present study, we show that Int6/eIF3e suppression affects cell proliferation, cell cycle and apoptosis of various GBM cells. We highlight that Int6 inhibition induces a diminution of proliferation through cell cycle arrest and increased apoptosis. Surprisingly, these phenotypes are independent of global cell translation inhibition and are accompanied by decreased HIF expression when Int6 is silenced. In conclusion, we demonstrate here that Int6/eIF3e is essential for proliferation and survival of GBM cells, presumably through modulation of the HIFs. |
| Databáze: | OpenAIRE |
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