Ets Factors Regulate Neural Stem Cell Depletion and Gliogenesis in Ras Pathway Glioma

Joshua J. Breunig, Rachelle Levy, C. Danielle Antonuk, Jessica Molina, Marina Dutra-Clarke, Hannah Park, Aslam Abbasi Akhtar, Gi Bum Kim, Xin Hu, Serguei I. Bannykh, Roel G.W. Verhaak, Moise Danielpour

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

As the list of putative driver mutations in glioma grows, we are just beginning to elucidate the effects of dysregulated developmental signaling pathways on the transformation of neural cells. We have employed a postnatal, mosaic, autochthonous glioma model that captures the first hours and days of gliomagenesis in more resolution than conventional genetically engineered mouse models of cancer. We provide evidence that disruption of the Nf1-Ras pathway in the ventricular zone at multiple signaling nodes uniformly results in rapid neural stem cell depletion, progenitor hyperproliferation, and gliogenic lineage restriction. Abolishing Ets subfamily activity, which is upregulated downstream of Ras, rescues these phenotypes and blocks glioma initiation. Thus, the Nf1-Ras-Ets axis might be one of the select molecular pathways that are perturbed for initiation and maintenance in glioma.

Original languageEnglish
Pages (from-to)258-271
Number of pages14
JournalCell Reports
Volume12
Issue number2
DOIs
StatePublished - 14 Jul 2015
Externally publishedYes

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