CHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming

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dc.citation.articleNumber2005047
dc.citation.issueNumber19
dc.citation.journalTitleAdvanced Science
dc.citation.volumeNumber8
dc.contributor.authorTao, Ling
dc.contributor.authorMoreno-Smith, Myrthala
dc.contributor.authorIbarra-García-Padilla, Rodrigo
dc.contributor.authorMilazzo, Giorgio
dc.contributor.authorDrolet, Nathan A.
dc.contributor.authorHernandez, Blanca E.
dc.contributor.authorOh, Young S.
dc.contributor.authorPatel, Ivanshi
dc.contributor.authorKim, Jean J.
dc.contributor.authorZorman, Barry
dc.contributor.authorPatel, Tajhal
dc.contributor.authorKamal, Abu Hena Mostafa
dc.contributor.authorZhao, Yanling
dc.contributor.authorHicks, John
dc.contributor.authorVasudevan, Sanjeev A.
dc.contributor.authorPutluri, Nagireddy
dc.contributor.authorCoarfa, Cristian
dc.contributor.authorSumazin, Pavel
dc.contributor.authorPerini, Giovanni
dc.contributor.authorParchem, Ronald J.
dc.contributor.authorUribe, Rosa A.
dc.contributor.authorBarbieri, Eveline
dc.date.accessioned2021-10-18T14:34:18Z
dc.date.available2021-10-18T14:34:18Z
dc.date.issued2021
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.
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.
dc.identifier.digitaladvs-202005047
dc.identifier.doihttps://doi.org/10.1002/advs.202005047
dc.identifier.urihttps://hdl.handle.net/1911/111547
dc.language.isoeng
dc.publisherWiley
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.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleCHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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