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The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors

Open access
Zingg, Daniel, Debbache, Julien, Schaefer, Simon M., Tuncer, Eylul, Frommel, Sandra C., Cheng, Phil, Arenas-Ramirez, Natalia, Haeusel, Jessica, Zhang, Yudong, Bonalli, Mario, McCabe, Michael T., Creasy, Caretha L., Levesque, Mitchell P., Boyman, Onur, Santoro, Raffaella, Shakhova, Olga, Dummer, Reinhard, Sommer, Lukas·2015·Nature Communications

Abstract

Increased activity of the epigenetic modifier EZH2 has been associated with different cancers. However, evidence for a functional role of EZH2 in tumorigenesis in vivo remains poor, in particular in metastasizing solid cancers. Here we reveal central roles of EZH2 in promoting growth and metastasis of cutaneous melanoma. In a melanoma mouse model, conditional Ezh2 ablation as much as treatment with the preclinical EZH2 inhibitor GSK503 stabilizes the disease through inhibition of growth and virtually abolishes metastases formation without affecting normal melanocyte biology. Comparably, in human melanoma cells, EZH2 inactivation impairs proliferation and invasiveness, accompanied by re-expression of tumour suppressors connected to increased patient survival. These EZH2 target genes suppress either melanoma growth or metastasis in vivo, revealing the dual function of EZH2 in promoting tumour progression. Thus, EZH2-mediated epigenetic repression is highly relevant especially during advanced melanoma progression, which makes EZH2 a promising target for novel melanoma therapies. The epigenetic modifier EZH2 is highly expressed in melanoma but its role in cancer initiation and progression is still unclear. Here the authors use mouse models and human cell lines to show that EZH2 has an essential role in melanoma progression and metastasis, thus highlighting its potential as a therapeutic target.

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Metadata

Authors
Zingg, D., Debbache, J., Schaefer, S. M., Tuncer, E., Frommel, S. C., Cheng, P., Arenas-Ramirez, N., Haeusel, J., Zhang, Y., Bonalli, M., McCabe, M. T., Creasy, C. L., Levesque, M. P., Boyman, O., Santoro, R., Shakhova, O., Dummer, R., & Sommer, L.
Venue
Nature Communications
Published
2015-01-22
Volume
6
Issue
1
Pages
6051-6051
ISSN
2041-1723 (ISSN-L)
OpenAlex
W1969485334
Cited by
334
References
8
FWCI
14.54
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors. https://app.cochat.ai/papers/10.1038/ncomms7051
The paper
Zingg, D., Debbache, J., Schaefer, S. M., Tuncer, E., Frommel, S. C., Cheng, P., Arenas-Ramirez, N., Haeusel, J., Zhang, Y., Bonalli, M., McCabe, M. T., Creasy, C. L., Levesque, M. P., Boyman, O., Santoro, R., Shakhova, O., Dummer, R., & Sommer, L. (2015). The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors. Nature Communications. https://doi.org/10.1038/ncomms7051

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.