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Accession IconGSE63165

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

Organism Icon Homo sapiens
Sample Icon 11 Downloadable Samples
Technology Badge Icon Affymetrix Human Gene 2.1 ST Array (hugene21st)

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Increased activity of the epigenetic modifier EZH2 has been associated with different cancers. However, evidence for a functional role of EZH2 in tumourigenesis in vivo remains poor, in particular in metastasising 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 stabilises 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 melanoma growth and prevent EMT / metastasis in vivo revealing the dual function of EZH2 in promoting tumour progression. Thus, EZH2-mediated epigenetic repression is highly relevant especially during advanced melanomagenesis, which makes EZH2 a promising target for novel melanoma therapies.
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