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Melanomas are one of the most aggressive types of tumors in humans, some patients may benefit from the new forms of immunotherapies but other patients may suffer recurrence of the disease after successful treatment. A team of researchers led by Lukas Sommer, professor at the Institute of Anatomy at the University of Zurich (UZH), has now been able to show that in addition to genetic causes such as mutations in the DNA, epigenetic factors also play a role in the formation and spread of melanoma.
Epigenetic factors do not directly influence the gene sequence, they regulate how efficiently certain genes are transcribed in the cells. The researchers focused on the EZH2 protein, which-unlike in benign cells is very common in melanoma cells and plays a central role in melanoma formation. EZH2 suppresses ciliary genes and leads to metastasis.
To find out how epigenetic factors contribute to the melanoma’s aggressive behavior, the scientists examined all the genes that are regulated by EZH2 and discovered that many genes are jointly responsible for the formation of cilia. Cilia genes are suppressed by EZH2, which means that malignant melanoma cells have much fewer of these fine sensory hairs than the skin’s benign pigment cells.
Using human melanoma cells and mouse models, the researchers succeeded in demonstrating that loss of cilia in pigment cells activates carcinogenic signaling pathways, resulting in the formation of aggressive, metastatic melanoma. The epigenetic regulation of cilia formation discovered in melanoma is relevant for the formation of other types of cancers, such as breast or brain tumors.
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