Journal
SCIENCE ADVANCES
Volume 7, Issue 26, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abd2781
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Funding
- Giovanni Armenise-Harvard Foundation
- My First AIRC Grant
- CARITRO
- program Investissements d'avenir [ANR-10-IAIHU-06]
- ICM foundation
- Allen Distinguished Investigator Award
- Roger De Spoelberch Prize
- Fondazione Pezcoller
- Fondazione Umberto Veronesi postdoctoral fellowship (il Dono di Rossana)
- Marie Curie fellowship [844677]
- China Scholarship Council
- Marie Curie Actions (MSCA) [844677] Funding Source: Marie Curie Actions (MSCA)
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The identity of the cell of origin determines the cancer subtype, progression, and prognosis. The Notch1 pathway plays a critical role in the initiation of group 3 medulloblastoma (MB).
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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