YAP1/TAZ drives ependymoma-like tumour formation in mice.
Nat Commun
; 11(1): 2380, 2020 05 13.
Article
en En
| MEDLINE
| ID: mdl-32404936
ABSTRACT
YAP1 gene fusions have been observed in a subset of paediatric ependymomas. Here we show that, ectopic expression of active nuclear YAP1 (nlsYAP5SA) in ventricular zone neural progenitor cells using conditionally-induced NEX/NeuroD6-Cre is sufficient to drive brain tumour formation in mice. Neuronal differentiation is inhibited in the hippocampus. Deletion of YAP1's negative regulators LATS1 and LATS2 kinases in NEX-Cre lineage in double conditional knockout mice also generates similar tumours, which are rescued by deletion of YAP1 and its paralog TAZ. YAP1/TAZ-induced mouse tumours display molecular and ultrastructural characteristics of human ependymoma. RNA sequencing and quantitative proteomics of mouse tumours demonstrate similarities to YAP1-fusion induced supratentorial ependymoma. Finally, we find that transcriptional cofactor HOPX is upregulated in mouse models and in human YAP1-fusion induced ependymoma, supporting their similarity. Our results show that uncontrolled YAP1/TAZ activity in neuronal precursor cells leads to ependymoma-like tumours in mice.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Neoplasias Encefálicas
/
Transactivadores
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Proteínas de Ciclo Celular
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Proteínas Adaptadoras Transductoras de Señales
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Ependimoma
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2020
Tipo del documento:
Article