Department of Molecular, Cell and Cancer Biology
Amino Acids, Peptides, and Proteins | Cancer Biology | Enzymes and Coenzymes | Molecular and Cellular Neuroscience | Neoplasms | Nervous System | Nucleic Acids, Nucleotides, and Nucleosides
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.
Cancer models, Cell proliferation, CNS cancer, Phosphorylation, Tumour-suppressor proteins
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DOI of Published Version
Eder N, Roncaroli F, Dolmart MC, Horswell S, Andreiuolo F, Flynn HR, Lopes AT, Claxton S, Kilday JP, Collinson L, Mao JH, Pietsch T, Thompson B, Snijders AP, Ultanir SK. YAP1/TAZ drives ependymoma-like tumour formation in mice. Nat Commun. 2020 May 13;11(1):2380. doi: 10.1038/s41467-020-16167-y. PMID: 32404936; PMCID: PMC7220953. Link to article on publisher's site
Eder N, Roncaroli F, Dolmart M, Horswell S, Andreiuolo F, Flynn HR, Lopes AT, Claxton S, Kilday J, Collinson L, Mao J, Pietsch T, Thompson B, Snijders AP, Ultanir SK. (2020). YAP1/TAZ drives ependymoma-like tumour formation in mice. Open Access Articles. https://doi.org/10.1038/s41467-020-16167-y. Retrieved from https://escholarship.umassmed.edu/oapubs/4256
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This work is licensed under a Creative Commons Attribution 4.0 License.
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