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

doi:10.1016/j.ccell.2015.10.008

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 tijdschrift › Artikel › peer review

80 Citaten (Scopus)

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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-2	Engels
Pagina's (van-tot)	730-742
Aantal pagina's	13
Tijdschrift	Cancer Cell
Volume	28
Nummer van het tijdschrift	6
DOI's	https://doi.org/10.1016/j.ccell.2015.10.008
Status	Gepubliceerd - 14 dec. 2015
Extern gepubliceerd	Ja

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title = "A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes",

abstract = "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.",

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

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doi = "10.1016/j.ccell.2015.10.008",

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AU - Giachino, Claudio

AU - Boulay, Jean Louis

AU - Ivanek, Robert

AU - Alvarado, Alvaro

AU - Tostado, Cristobal

AU - Lugert, Sebastian

AU - Tchorz, Jan

AU - Coban, Mustafa

AU - Mariani, Luigi

AU - Bettler, Bernhard

AU - Lathia, Justin

AU - Frank, Stephan

AU - Pfister, Stefan

AU - Kool, Marcel

AU - Taylor, Verdon

PY - 2015/12/14

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N2 - 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.

AB - 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.

KW - Brain tumor

KW - Glioma

KW - Hes5

KW - Notch signaling

KW - Primitive neuroectodermal tumor

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A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes

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