Ricci, B;
Millner, TO;
Pomella, N;
Zhang, X;
Guglielmi, L;
Badodi, S;
Ceric, D;
... Marino, S; + view all
(2020)
Polycomb-mediated repression of EphrinA5 promotes growth and invasion of glioblastoma.
Oncogene
10.1038/s41388-020-1161-3.
(In press).
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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.
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