Research ArticleCancer

Transcriptional repressor REST drives lineage stage–specific chromatin compaction at Ptch1 and increases AKT activation in a mouse model of medulloblastoma

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Science Signaling  22 Jan 2019:
Vol. 12, Issue 565, eaan8680
DOI: 10.1126/scisignal.aan8680

Targeting SHH-type medulloblastoma

Medulloblastoma is a brain tumor that occurs mostly in children and has few therapeutic options. Attempts to block the Sonic Hedgehog (SHH) pathway that drives various subtypes of the tumor have been unsuccessful clinically. Dobson et al. found a mechanism by which SHH signaling may be increased in some patients. In a new mouse model, the authors found that increased expression of the transcriptional repressor REST in cells that give rise to the disease supports a more aggressive disease course by promoting epigenetic repression of the genes that encode PTCH1 and PTEN, thereby enhancing proliferative and migratory signaling by SHH and the kinase AKT. These findings reveal potential therapeutic targets for patients with high-REST, SHH-type medulloblastoma.

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