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Int6/eIF3e Is Essential for Proliferation and Survival of Human Glioblastoma Cells
INSERM U1037, Centre de Recherche en Cancérologie de Toulouse, 20-24 Rue du Pont St Pierre, 31052 Toulouse, Cedex, France
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Radiothérapie Institut Claudius Regaud, 20-24 Rue du Pont St Pierre, 31052 Toulouse, Cedex, France
* Author to whom correspondence should be addressed.
Received: 17 November 2013; in revised form: 25 December 2013 / Accepted: 23 January 2014 / Published: 29 January 2014
Abstract: 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.
Keywords: glioma; glioblastoma; proliferation; apoptosis; eukaryotic translation initiation factor; Int6; eIF3e; Hypoxia Inducible Factors; HIF-1α; HIF-2α
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Sesen, J.; Cammas, A.; Scotland, S.J.; Elefterion, B.; Lemarié, A.; Millevoi, S.; Mathew, L.K.; Seva, C.; Toulas, C.; Moyal, E.C.-J.; Skuli, N. Int6/eIF3e Is Essential for Proliferation and Survival of Human Glioblastoma Cells. Int. J. Mol. Sci. 2014, 15, 2172-2190.
Sesen J, Cammas A, Scotland SJ, Elefterion B, Lemarié A, Millevoi S, Mathew LK, Seva C, Toulas C, Moyal EC-J, Skuli N. Int6/eIF3e Is Essential for Proliferation and Survival of Human Glioblastoma Cells. International Journal of Molecular Sciences. 2014; 15(2):2172-2190.
Sesen, Julie; Cammas, Anne; Scotland, Sarah J.; Elefterion, Bertand; Lemarié, Anthony; Millevoi, Stefania; Mathew, Lijoy K.; Seva, Cathy; Toulas, Christine; Moyal, Elizabeth C.-J.; Skuli, Nicolas. 2014. "Int6/eIF3e Is Essential for Proliferation and Survival of Human Glioblastoma Cells." Int. J. Mol. Sci. 15, no. 2: 2172-2190.