UMMS Affiliation

Department of Molecular, Cell and Cancer Biology

Publication Date

2020-05-13

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Cancer Biology | Enzymes and Coenzymes | Molecular and Cellular Neuroscience | Neoplasms | Nervous System | Nucleic Acids, Nucleotides, and Nucleosides

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.

Keywords

Cancer models, Cell proliferation, CNS cancer, Phosphorylation, Tumour-suppressor proteins

Rights and Permissions

© The Author(s) 2020. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

DOI of Published Version

10.1038/s41467-020-16167-y

Source

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

Journal/Book/Conference Title

Nature communications

Related Resources

Link to Article in PubMed

PubMed ID

32404936

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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