Truncated BRPF1 Cooperates with Smoothened to Promote Adult Shh Medulloblastoma.
Cell Rep
; 29(12): 4036-4052.e10, 2019 12 17.
Article
em En
| MEDLINE
| ID: mdl-31851932
ABSTRACT
The transition of neural progenitors to differentiated postmitotic neurons is mainly considered irreversible in physiological conditions. In the present work, we show that Shh pathway activation through SmoM2 expression promotes postmitotic neurons dedifferentiation, re-entering in the cell cycle and originating medulloblastoma in vivo. Notably, human adult patients present inactivating mutations of the chromatin reader BRPF1 that are associated with SMO mutations and absent in pediatric and adolescent patients. Here, we found that truncated BRPF1 protein, as found in human adult patients, is able to induce medulloblastoma in adult mice upon SmoM2 activation. Indeed, postmitotic neurons re-entered the cell cycle and proliferated as a result of chromatin remodeling of neurons by BRPF1. Our model of brain cancer explains the onset of a subset of human medulloblastoma in adult individuals where granule neuron progenitors are no longer present.
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MEDLINE
Assunto principal:
Neoplasias Cerebelares
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas de Ligação a DNA
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Proteínas Hedgehog
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Receptor Smoothened
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Meduloblastoma
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Mutação
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Neurônios
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article