Polycomb-mediated repression of EphrinA5 promotes growth and invasion of glioblastoma

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 l...

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Detalles Bibliográficos
Autores principales: Ricci, Barbara, Millner, Thomas O., Pomella, Nicola, Zhang, Xinyu, Guglielmi, Loredana, Badodi, Sara, Ceric, Dario, Gemma, Carolina, Cognolato, Erica, Zhang, Ying, Brandner, Sebastian, Barnes, Michael R., Marino, Silvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082224/
https://www.ncbi.nlm.nih.gov/pubmed/31988455
http://dx.doi.org/10.1038/s41388-020-1161-3
Descripción
Sumario: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.

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