Polycomb-mediated repression of EphrinA5 promotes growth and invasion of glioblastoma.
Oncogene
; 39(12): 2523-2538, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-31988455
ABSTRACT
Glioblastoma (GBM) is the most common and most aggressive intrinsic brain tumour in adults. Integrated transcriptomic and epigenomic analyses of glioblastoma initiating cells (GIC) in a mouse model uncovered a novel epigenetic regulation of EfnA5. In this model, Bmi1 enhances H3K27me3 at the EfnA5 locus and reinforces repression of selected target genes in a cellular context-dependent fashion. EfnA5 mediates Bmi1-dependent proliferation and invasion in vitro and tumour formation in an allograft model. Importantly, we show that this novel Polycomb feed-forward loop is also active in human GIC and we provide pre-clinical evidence of druggability of the EFNA5 signalling pathway in GBM xenografts overexpressing Bmi1.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glioblastoma
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Efrina-A5
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Complexo Repressor Polycomb 1
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Oncogene
Ano de publicação:
2020
Tipo de documento:
Article