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A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes

Claudio Giachino1, Jean-Louis Boulay2, Robert Ivanek1

  • 1Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland.

Cancer Cell
|December 17, 2015
PubMed

Insights

Notch signaling unexpectedly suppresses brain tumors, contrary to its known cancer-promoting role. Activating Notch reduced glioma growth and improved survival in mice and humans, highlighting its potential as a therapeutic target.

Area of Science:

  • Neuro-oncology
  • Molecular biology
  • Cancer stem cell research

Background:

  • Notch signaling is known to maintain neural stem cells and promote brain cancer stem cells.
  • Its precise role in different brain tumor subtypes remained unclear.

Purpose of the Study:

  • To investigate the role of Notch signaling in specific forebrain tumor subtypes.
  • To determine if Notch signaling has a tumor suppressor function in gliomas.

Main Methods:

  • Genetic inactivation of Notch pathway components (RBP-Jκ, Notch1, Notch2) in PDGF-driven mouse glioma models.
  • Genetic activation of the Notch pathway in mouse glioma models.
  • Correlation analysis of Notch activity with human glioma subtypes, survival, and tumor grade.
  • Investigating Notch cooperation with p53 in tumor development.

Main Results:

  • Inactivating Notch signaling accelerated glioma growth in mice.
  • Activating Notch signaling reduced glioma growth and increased survival in mice.
  • High Notch activity correlated with specific human glioma subtypes, better patient survival, and lower tumor grade.
  • Notch signaling cooperates with p53 to restrict tumor growth.

Conclusions:

  • Notch signaling acts as a tumor suppressor in certain forebrain tumor subtypes, including gliomas.
  • Notch pathway activation demonstrates therapeutic potential for glioma treatment.
  • Notch signaling is a critical regulator of brain tumor development, cooperating with p53.
Keywords:
Hes5Notch signalingbrain tumorgliomaprimitive neuroectodermal tumor

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