Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/57876
Registo completo
Campo DC | Valor | Idioma |
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dc.contributor.author | Mancini, Andrew | por |
dc.contributor.author | Magalhães, Ana Xavier Silva | por |
dc.contributor.author | Woods, Wendy S. | por |
dc.contributor.author | Nguyen, Kien-Thiet | por |
dc.contributor.author | Amen, Alexandra M. | por |
dc.contributor.author | Hayes, Josie L. | por |
dc.contributor.author | Fellmann, Christof | por |
dc.contributor.author | Gapinske, Michael | por |
dc.contributor.author | McKinney, Andrew M. | por |
dc.contributor.author | Hong, Chibo | por |
dc.contributor.author | Jones, Lindsey E. | por |
dc.contributor.author | Walsh, Kyle M. | por |
dc.contributor.author | Bell, Robert J. A. | por |
dc.contributor.author | Doudna, Jennifer A. | por |
dc.contributor.author | Costa, Bruno Marques | por |
dc.contributor.author | Song, Jun S. | por |
dc.contributor.author | Perez-Pinera, Pablo | por |
dc.contributor.author | Costello, Joseph F. | por |
dc.date.accessioned | 2019-01-07T17:04:27Z | - |
dc.date.available | 2019-09-10T06:00:14Z | - |
dc.date.issued | 2018-09-10 | - |
dc.identifier.citation | Mancini, A., Xavier-Magalhães, A., Woods, W. S., et. al.(2018). Disruption of the β1L isoform of GABP reverses glioblastoma replicative immortality in a TERT promoter mutation-dependent manner. Cancer cell, 34(3), 513-528 | por |
dc.identifier.issn | 1535-6108 | - |
dc.identifier.uri | https://hdl.handle.net/1822/57876 | - |
dc.description.abstract | TERT promoter mutations reactivate telomerase, allowing for indefinite telomere maintenance and enabling cellular immortalization. These mutations specifically recruit the multimeric ETS factor GABP, which can form two functionally independent transcription factor species: a dimer or a tetramer. We show that genetic disruption of GABPβ1L (β1L), a tetramer-forming isoform of GABP that is dispensable for normal development, results in TERT silencing in a TERT promoter mutation-dependent manner. Reducing TERT expression by disrupting β1L culminates in telomere loss and cell death exclusively in TERT promoter mutant cells. Orthotopic xenografting of β1L-reduced, TERT promoter mutant glioblastoma cells rendered lower tumor burden and longer overall survival in mice. These results highlight the critical role of GABPβ1L in enabling immortality in TERT promoter mutant glioblastoma. | por |
dc.description.sponsorship | This work was supported by a generous gift from the Dabbiere family (J.F.C.), the Hana Jabsheh Research Initiative (J.F.C.), NIH grant NCI P50CA097257 (J.F.C. and J.A.D.), NCI P01CA118816-06 (J.F.C.), T32 GM008568 and T32 CA151022 (A.M.), and NCI R01CA163336 (J.S.S.), and the Sontag Foundation Distinguished Scientist Award (J.S.S.). C.F. is supported by a US NIH K99/R00 Pathway to Independence Award (K99GM118909) from the National Institute of General Medical Sciences. Additional support was provided by Fundação para a Ciência e Tecnologia SFRH/BD/88220/2012 (A.X.-M.) and IF/00601/2012 (B.M.C.). J.A.D. is an investigator of the Howard Hughes Medical Institute. | por |
dc.language.iso | eng | por |
dc.publisher | Elsevier 1 | por |
dc.relation | info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F88220%2F2012/PT | - |
dc.rights | openAccess | por |
dc.subject | Glioblastoma | por |
dc.subject | TERT promoter mutation | por |
dc.subject | GABP | por |
dc.subject | Cancer immortality | por |
dc.subject | Telomerase | por |
dc.subject | Telomeres | por |
dc.title | Disruption of the β1L Isoform of GABP Reverses Glioblastoma Replicative Immortality in a TERT Promoter Mutation-Dependent Manner | por |
dc.type | article | por |
dc.peerreviewed | yes | por |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S153561081830357X | por |
oaire.citationStartPage | 513 | por |
oaire.citationEndPage | 528.e8 | por |
oaire.citationIssue | 3 | por |
oaire.citationVolume | 34 | por |
dc.identifier.doi | 10.1016/j.ccell.2018.08.003 | por |
dc.identifier.pmid | 30205050 | por |
dc.subject.fos | Ciências Médicas::Medicina Básica | por |
dc.description.publicationversion | info:eu-repo/semantics/publishedVersion | por |
dc.subject.wos | Science & Technology | por |
sdum.journal | Cancer Cell | por |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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mancini2018.pdf | 5,17 MB | Adobe PDF | Ver/Abrir |