CHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming

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dc.citation.articleNumber2005047en_US
dc.citation.issueNumber19en_US
dc.citation.journalTitleAdvanced Scienceen_US
dc.citation.volumeNumber8en_US
dc.contributor.authorTao, Lingen_US
dc.contributor.authorMoreno-Smith, Myrthalaen_US
dc.contributor.authorIbarra-García-Padilla, Rodrigoen_US
dc.contributor.authorMilazzo, Giorgioen_US
dc.contributor.authorDrolet, Nathan A.en_US
dc.contributor.authorHernandez, Blanca E.en_US
dc.contributor.authorOh, Young S.en_US
dc.contributor.authorPatel, Ivanshien_US
dc.contributor.authorKim, Jean J.en_US
dc.contributor.authorZorman, Barryen_US
dc.contributor.authorPatel, Tajhalen_US
dc.contributor.authorKamal, Abu Hena Mostafaen_US
dc.contributor.authorZhao, Yanlingen_US
dc.contributor.authorHicks, Johnen_US
dc.contributor.authorVasudevan, Sanjeev A.en_US
dc.contributor.authorPutluri, Nagireddyen_US
dc.contributor.authorCoarfa, Cristianen_US
dc.contributor.authorSumazin, Pavelen_US
dc.contributor.authorPerini, Giovannien_US
dc.contributor.authorParchem, Ronald J.en_US
dc.contributor.authorUribe, Rosa A.en_US
dc.contributor.authorBarbieri, Evelineen_US
dc.date.accessioned2021-10-18T14:34:18Zen_US
dc.date.available2021-10-18T14:34:18Zen_US
dc.date.issued2021en_US
dc.description.abstractNeuroblastoma (NB) arises from oncogenic disruption of neural crest (NC) differentiation. Treatment with retinoic acid (RA) to induce differentiation has improved survival in some NB patients, but not all patients respond, and most NBs eventually develop resistance to RA. Loss of the chromatin modifier chromatin assembly factor 1 subunit p150 (CHAF1A) promotes NB cell differentiation; however, the mechanism by which CHAF1A drives NB oncogenesis has remained unexplored. This study shows that CHAF1A gain-of-function supports cell malignancy, blocks neuronal differentiation in three models (zebrafish NC, human NC, and human NB), and promotes NB oncogenesis. Mechanistically, CHAF1A upregulates polyamine metabolism, which blocks neuronal differentiation and promotes cell cycle progression. Targeting polyamine synthesis promotes NB differentiation and enhances the anti-tumor activity of RA. The authors' results provide insight into the mechanisms that drive NB oncogenesis and suggest a rapidly translatable therapeutic approach (DFMO plus RA) to enhance the clinical efficacy of differentiation therapy in NB patients.en_US
dc.identifier.citationTao, Ling, Moreno-Smith, Myrthala, Ibarra-García-Padilla, Rodrigo, et al.. "CHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming." <i>Advanced Science,</i> 8, no. 19 (2021) Wiley: https://doi.org/10.1002/advs.202005047.en_US
dc.identifier.digitaladvs-202005047en_US
dc.identifier.doihttps://doi.org/10.1002/advs.202005047en_US
dc.identifier.urihttps://hdl.handle.net/1911/111547en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.rightsThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleCHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogrammingen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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