A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes

Claudio Giachino, Jean Louis Boulay, Robert Ivanek, Alvaro Alvarado, Cristobal Tostado, Sebastian Lugert, Jan Tchorz, Mustafa Coban, Luigi Mariani, Bernhard Bettler, Justin Lathia, Stephan Frank, Stefan Pfister, Marcel Kool, Verdon Taylor

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

74 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)730-742
Aantal pagina's13
TijdschriftCancer Cell
Volume28
Nummer van het tijdschrift6
DOI's
StatusGepubliceerd - 14 dec. 2015
Extern gepubliceerdJa

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