Notch1 switches progenitor competence in inducing medulloblastoma
The identity of the cell of origin is a key determinant of cancer subtype, progression, and prognosis. Group 3 medulloblastoma (MB) is a malignant childhood brain cancer with poor prognosis and few candidates as putative cell of origin. We overexpressed the group 3 MB genetic drivers MYC and Gfi1 in...
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| Hauptverfasser: | , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
23 Jun 2021
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| In: |
Science advances
Year: 2021, Jahrgang: 7, Heft: 26, Pages: 1-13 |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.abd2781 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1126/sciadv.abd2781 Verlag, lizenzpflichtig, Volltext: https://www.webofscience.com/api/gateway?GWVersion=2&SrcAuth=DynamicDOIArticle&SrcApp=WOS&KeyAID=10.1126%2Fsciadv.abd2781&DestApp=DOI&SrcAppSID=EUW1ED0A6DWkauDRZWxohELriO3fR&SrcJTitle=SCIENCE+ADVANCES&DestDOIRegistrantName=American+Association+for+the+Advancement+of+Science+%28AAAS%29 
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| Verfasserangaben: | Claudio Ballabio, Matteo Gianesello, Chiara Lago, Konstantin Okonechnikov, Marica Anderle, Giuseppe Aiello, Francesco Antonica, Tingting Zhang, Francesca Gianno, Felice Giangaspero, Bassem A. Hassan, Stefan M. Pfister, Luca Tiberi |
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| 245 | 1 | 0 | |a Notch1 switches progenitor competence in inducing medulloblastoma |c Claudio Ballabio, Matteo Gianesello, Chiara Lago, Konstantin Okonechnikov, Marica Anderle, Giuseppe Aiello, Francesco Antonica, Tingting Zhang, Francesca Gianno, Felice Giangaspero, Bassem A. Hassan, Stefan M. Pfister, Luca Tiberi |
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| 520 | |a The identity of the cell of origin is a key determinant of cancer subtype, progression, and prognosis. Group 3 medulloblastoma (MB) is a malignant childhood brain cancer with poor prognosis and few candidates as putative cell of origin. We overexpressed the group 3 MB genetic drivers MYC and Gfi1 in different candidate cells of origin in the postnatal mouse cerebellum. We found that S100b(+) cells are competent to initiate group 3 MB, and we observed that S100b(+) cells have higher levels of Notch1 pathway activity compared to Math1(+) cells. We found that additional activation of Notch1 in Math1(+) and Sox2(+) cells was sufficient to induce group 3 MB upon MYC/Gfi1 expression. Together, our data suggest that the Notch1 pathway plays a critical role in group 3 MB initiation. | ||
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