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

Oncogene 2020 Mar

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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.

Citation

Barbara Ricci, Thomas O Millner, Nicola Pomella, Xinyu Zhang, Loredana Guglielmi, Sara Badodi, Dario Ceric, Carolina Gemma, Erica Cognolato, Ying Zhang, Sebastian Brandner, Michael R Barnes, Silvia Marino. Polycomb-mediated repression of EphrinA5 promotes growth and invasion of glioblastoma. Oncogene. 2020 Mar;39(12):2523-2538