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dc.contributor.authorHeynen, Guus J.J.E.
dc.contributor.authorNevedomskaya, Ekaterina
dc.contributor.authorPalit, Sander
dc.contributor.authorBasheer, Noorjahan Jagalur
dc.contributor.authorLieftink, Cor
dc.contributor.authorSchlicker, Andreas
dc.contributor.authorZwart, Wilbert
dc.contributor.authorBernards, René
dc.contributor.authorBajpe, Prashanth Kumar
dc.contributor.illustrator
dc.date.accessioned2020-11-26T11:09:33Z
dc.date.available2020-11-26T11:09:33Z
dc.date.issued2016-01-19
dc.identifier.citationHeynen G, Nevedomskaya E, Palit S, Basheer N, Lieftink C, Schlicker A, Zwart W, Bernards R, Bajpe P (2016) 'Mastermind-Like 3 controls proliferation and differentiation in neuroblastoma', Molecular Cancer Research, 14 (5), pp.411-422.en_US
dc.identifier.issn1541-7786
dc.identifier.pmid26785999
dc.identifier.doi10.1158/1541-7786.MCR-15-0291-T
dc.identifier.urihttp://hdl.handle.net/10547/624674
dc.description.abstractNeuroblastoma cell lines can differentiate upon treatment with retinoic acid (RA), a finding that provided the basis for the clinical use of RA to treat neuroblastoma. However, resistance to RA is often observed, which limits its clinical utility. Using a gain-of-function genetic screen, we identified an unexpected link between RA signaling and mastermindlike 3 (MAML3), a known transcriptional coactivator for NOTCH. Our findings indicate that MAML3 expression leads to the loss of activation of a subset of RA target genes, which hampers RA-induced differentiation and promotes resistance to RA. The regulatory DNA elements of this subset of RA target genes show overlap in binding of MAML3 and the RA receptor, suggesting a direct role for MAML3 in the regulation of these genes. In addition, MAML3 has RA-independent functions, including the activation of IGF1R and downstream AKT signaling via upregulation of IGF2, resulting in increased proliferation. These results demonstrate an important mechanistic role for MAML3 in proliferation and RA-mediated differentiation.en_US
dc.language.isoenen_US
dc.publisherAmerican Association for Cancer Research Inc.en_US
dc.relation.urlhttps://mcr.aacrjournals.org/content/14/5/411.longen_US
dc.rightsYellow - can archive pre-print (ie pre-refereeing)
dc.subjectneuroblastomaen_US
dc.titleMastermind-Like 3 controls proliferation and differentiation in neuroblastomaen_US
dc.typeArticleen_US
dc.contributor.departmentNetherlands Cancer Institute,en_US
dc.contributor.departmentErasmus Medical Center/Sophia Children's Hospitalen_US
dc.identifier.journalMolecular Cancer Researchen_US
dc.date.updated2020-11-26T10:55:57Z
dc.description.notefile is final published version, not to be passed to repository


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