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.
Notch1 switches progenitor competence in inducing medulloblastoma / Ballabio, C.; Gianesello, M.; Lago, C.; Okonechnikov, K.; Anderle, M.; Aiello, G.; Antonica, F.; Zhang, T.; Gianno, F.; Giangaspero, F.; Hassan, B. A.; Pfister, S. M.; Tiberi, L.. - In: SCIENCE ADVANCES. - ISSN 2375-2548. - 7:26(2021). [10.1126/sciadv.abd2781]
Notch1 switches progenitor competence in inducing medulloblastoma
Gianno F.;Giangaspero F.;Tiberi L.
Ultimo
2021
Abstract
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.| File | Dimensione | Formato | |
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Ballabio_Notch1 switches_2021.pdf
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