Polycomb-mediated repression of EphrinA5 promotes growth and invasion of glioblastoma.
Barbara RicciThomas O MillnerNicola PomellaXinyu ZhangLoredana GuglielmiSara BadodiDario CericCarolina GemmaErica CognolatoYing ZhangSebastian BrandnerMichael R BarnesSilvia MarinoPublished in: Oncogene (2020)
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.
Keyphrases
- body mass index
- mouse model
- weight gain
- induced apoptosis
- endothelial cells
- cell cycle arrest
- single cell
- genome wide
- white matter
- transcription factor
- induced pluripotent stem cells
- cell migration
- gene expression
- resting state
- cell death
- brain injury
- signaling pathway
- subarachnoid hemorrhage
- genome wide identification