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dc.contributor.authorSimoes-Sousa, Susana
dc.contributor.authorLittler, Samantha
dc.contributor.authorThompson, Sarah L
dc.contributor.authorMinshall, Paul
dc.contributor.authorWhalley, Helen J
dc.contributor.authorBakker, B
dc.contributor.authorBelkot, Klaudyna
dc.contributor.authorMoralli, D
dc.contributor.authorBronder, Daniel
dc.contributor.authorTighe, Anthony
dc.contributor.authorSpierings, DCJ
dc.contributor.authorBah, Nourdine
dc.contributor.authorGraham, Joshua
dc.contributor.authorNelson, Louisa
dc.contributor.authorGreen, CM
dc.contributor.authorFoijer, F
dc.contributor.authorTownsend, Paul A
dc.contributor.authorTaylor, Stephen S
dc.date.accessioned2018-12-10T13:46:16Z
dc.date.available2018-12-10T13:46:16Z
dc.date.issued2018en
dc.identifier.citationSimoes-Sousa S, Littler S, Thompson SL, Minshall P, Whalley H, Bakker B, et al. The p38 alpha stress kinase suppresses aneuploidy tolerance by inhibiting Hif-1 alpha. Cell Rep. 2018 Oct 16;25(3):749-60 e6.en
dc.identifier.pmid30332653en
dc.identifier.doi10.1016/j.celrep.2018.09.060en
dc.identifier.urihttp://hdl.handle.net/10541/621430
dc.description.abstractDeviating from the normal karyotype dramatically changes gene dosage, in turn decreasing the robustness of biological networks. Consequently, aneuploidy is poorly tolerated by normal somatic cells and acts as a barrier to transformation. Paradoxically, however, karyotype heterogeneity drives tumor evolution and the emergence of therapeutic drug resistance. To better understand how cancer cells tolerate aneuploidy, we focused on the p38 stress response kinase. We show here that p38-deficient cells upregulate glycolysis and avoid post-mitotic apoptosis, leading to the emergence of aneuploid subclones. We also show that p38 deficiency upregulates the hypoxia-inducible transcription factor Hif-1? and that inhibiting Hif-1? restores apoptosis in p38-deficent cells. Because hypoxia and aneuploidy are both barriers to tumor progression, the ability of Hif-1? to promote cell survival following chromosome missegregation raises the possibility that aneuploidy tolerance coevolves with adaptation to hypoxia.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/ 10.1016/j.celrep.2018.09.060en
dc.titleThe p38 alpha stress kinase suppresses aneuploidy tolerance by inhibiting Hif-1 alpha.en
dc.typeArticleen
dc.contributor.departmentDivision of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Cancer Research Centre, Wilmslow Road, Manchester M20 4QLen
dc.identifier.journalCell Reportsen


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