Characterization of the transcriptional and metabolic responses of pediatric high grade gliomas to mTOR-HIF-1a...

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dc.citation.epage71617en_US
dc.citation.issueNumber42en_US
dc.citation.spage71597en_US
dc.citation.volumeNumber8en_US
dc.contributor.authorNguyen, A.en_US
dc.contributor.authorMoussallieh, F. M.en_US
dc.contributor.authorMackay, A.en_US
dc.contributor.authorCicek, A. E.en_US
dc.contributor.authorCoca, A.en_US
dc.contributor.authorChenard, M. P.en_US
dc.contributor.authorWeingertner, N.en_US
dc.contributor.authorLhermitte, B.en_US
dc.contributor.authorLetouzé, E.en_US
dc.contributor.authorGuérin, E.en_US
dc.contributor.authorPencreach, E.en_US
dc.contributor.authorJannier, S.en_US
dc.contributor.authorGuenot, D.en_US
dc.contributor.authorNamer, I. J.en_US
dc.contributor.authorJones, C.en_US
dc.contributor.authorEntz-Werlé, N.en_US
dc.date.accessioned2019-02-13T06:45:14Z
dc.date.available2019-02-13T06:45:14Z
dc.date.issued2017-03-23en_US
dc.departmentDepartment of Computer Engineeringen_US
dc.description.abstractPediatric high grade glioma (pHGGs), including sus-tentorial and diffuse intrinsic pontine gliomas, are known to have a very dismal prognosis. For instance, even an increased knowledge on molecular biology driving this brain tumor entity, there is no treatment able to cure those patients. Therefore, we were focusing on a translational pathway able to increase the cell resistance to treatment and to reprogram metabolically tumor cells, which are, then, adapting easily to a hypoxic microenvironment. To establish, the crucial role of the hypoxic pathways in pHGGs, we, first, assessed their protein and transcriptomic deregulations in a pediatric cohort of pHGGs and in pHGG’s cell lines, cultured in both normoxic and hypoxic conditions. Secondly, based on the concept of a bi-therapy targeting in pHGGs mTORC1 (rapamycin) and HIF-1α (irinotecan), we hypothesized that the balanced expressions between RAS/ERK, PI3K/AKT and HIF-1α/HIF-2α/MYC proteins or genes may provide a modulation of the cell response to this double targeting. Finally, we could evidence three protein, genomic and metabolomic profiles of response to rapamycin combined with irinotecan. The pattern of highly sensitive cells to mTOR/HIF-1α targeting was linked to a MYC/ERK/HIF-1α over-expression and the cell resistance to a major hyper-expression of HIF-2α.en_US
dc.identifier.doi10.18632/oncotarget.16500en_US
dc.identifier.eissn1949-2553
dc.identifier.urihttp://hdl.handle.net/11693/49371
dc.language.isoEnglishen_US
dc.publisherImpact Journals LLCen_US
dc.relation.isversionofhttp://doi.org/10.18632/oncotarget.16500en_US
dc.source.titleOncoTargeten_US
dc.subjectHIF1alphaen_US
dc.subjectHigh grade gliomaen_US
dc.subjectmToren_US
dc.subjectPediatricen_US
dc.subjectTargetsen_US
dc.titleCharacterization of the transcriptional and metabolic responses of pediatric high grade gliomas to mTOR-HIF-1a...en_US
dc.typeArticleen_US

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