Cancer Cell
Volume 28, Issue 6, 14 December 2015, Pages 730-742
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Article
A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes

https://doi.org/10.1016/j.ccell.2015.10.008 Get rights and content
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Highlights

  • Notch signaling and p53 cooperate to reduce initiation of forebrain tumor subtypes

  • Anti-tumorigenic effects of Notch are linked to regulation of quiescence

  • Inhibiting Notch promotes a primitive neuroectodermal-like tumor fate

  • Low Notch activity correlates with poor prognosis for patients with glioma subtypes

Summary

In the brain, Notch signaling maintains normal neural stem cells, but also brain cancer stem cells, indicating an oncogenic role. Here, we identify an unexpected tumor suppressor function for Notch in forebrain tumor subtypes. Genetic inactivation of RBP-Jκ, a key Notch mediator, or Notch1 and Notch2 receptors accelerates PDGF-driven glioma growth in mice. Conversely, genetic activation of the Notch pathway reduces glioma growth and increases survival. In humans, high Notch activity strongly correlates with distinct glioma subtypes, increased patient survival, and lower tumor grade. Additionally, simultaneous inactivation of RBP-Jκ and p53 induces primitive neuroectodermal-like tumors in mice. Hence, Notch signaling cooperates with p53 to restrict cell proliferation and tumor growth in mouse models of human brain tumors.

Keywords

brain tumor
glioma
primitive neuroectodermal tumor
Notch signaling
Hes5

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