dc.contributor.author | Ali, Fahad R. | |
dc.contributor.author | Marcos Corchado, Daniel | |
dc.contributor.author | Chernukhin, Igor | |
dc.contributor.author | Woods, Laura M. | |
dc.contributor.author | Parkinson, Lydia M. | |
dc.contributor.author | Wylie, Luke A. | |
dc.contributor.author | Papkovskaia, Tatiana D. | |
dc.contributor.author | Davies, John D. | |
dc.contributor.author | Carroll, Jason S. | |
dc.contributor.author | Philpott, Anna | |
dc.date.accessioned | 2023-12-07T10:48:39Z | |
dc.date.available | 2023-12-07T10:48:39Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 1541-7786 | spa |
dc.identifier.uri | https://hdl.handle.net/10641/3550 | |
dc.description.abstract | Pediatric cancers often resemble trapped developmental intermediate states that fail to engage the normal differentiation program, typified by high-risk neuroblastoma arising from the developing sympathetic nervous system. Neuroblastoma cells resemble arrested neuroblasts trapped by a stable but aberrant epigenetic program controlled by sustained expression of a core transcriptional circuit of developmental regulators in conjunction with elevated MYCN or MYC (MYC). The transcription factor ASCL1 is a key master regulator in neuroblastoma and has oncogenic and tumor-suppressive activities in several other tumor types. Using functional mutational approaches, we find that preventing CDK-dependent phosphorylation of ASCL1 in neuroblastoma cells drives coordinated suppression of the MYC-driven core circuit supporting neuroblast identity and proliferation, while simultaneously activating an enduring gene program driving mitotic exit and neuronal differentiation.
Implications:
These findings indicate that targeting phosphorylation of ASCL1 may offer a new approach to development of differentiation therapies in neuroblastoma. | spa |
dc.language.iso | eng | spa |
dc.publisher | Molecular Cancer Research | spa |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.title | Dephosphorylation of the Proneural Transcription Factor ASCL1 Re-Engages a Latent Post-Mitotic Differentiation Program in Neuroblastoma. | spa |
dc.type | journal article | spa |
dc.type.hasVersion | AM | spa |
dc.rights.accessRights | open access | spa |
dc.description.extent | 1604 KB | spa |
dc.identifier.doi | 10.1158/1541-7786.MCR-20-0693 | spa |
dc.relation.publisherversion | https://aacrjournals.org/mcr/article/18/12/1759/90073/Dephosphorylation-of-the-Proneural-Transcription | spa |