Melanoma and Loss of Cilia Linked

The epigenetic regulation of cilia formation plays a key role in melanoma, revealed study.

Loss of cilia in pigment cells activates carcinogenic signaling pathways, resulting in the formation of aggressive, metastatic melanoma, found study.

Melanomas are one of the most aggressive types of tumors in humans. Despite remarkable success with new forms of treatment such as immunotherapies, there are still many melanoma patients who cannot be cured or who later suffer a recurrence of the disease following successful treatment. An in-depth understanding of the tumor's biology is thus essential for developing novel therapeutic approaches. The main question is which changes in a benign cell cause it to progress into a malignant tumor.

Melanoma - Causes, Symptoms, Diagnosis, Treatment & Prevention
Melanoma of the skin is a dangerous type of skin cancer that usually appears as a cancerous mole due to exposure to the sun’s damaging UV rays.

‘The epigenetic regulation of cilia formation plays a key role in melanoma.’

Formation and spread of melanoma also regulated epigenetically

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. While epigenetic factors don't directly influence the gene sequence, they do regulate how efficiently certain genes are transcribed in the cells. The UZH 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

Test your Knowledge on Moles and Melanoma
Melanoma is a skin condition that is often a consequence of excessive exposure to the sun’s ultraviolet radiation. Test your knowledge on melanoma by taking this quiz.

To find out how epigenetic factors contribute to the melanoma's aggressive behavior, the scientists examined all the genes that are regulated by EZH2. "We were very surprised to find many genes that are jointly responsible for the formation of cilia," says study leader Sommer. It seems that 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.

Approach for novel tumor therapies

Study Uncovers Factors That Cause Melanoma Metastasis
Direct contact with lymphatic endothelial cells promotes melanoma metastasis, shows new study.

There are many types of cancers composed of cells that have lost their cilia. "The epigenetic regulation of cilia formation that we've now discovered in melanoma is, therefore, likely also relevant for the formation of other types of cancers, such as breast or brain tumors," remarks Lukas Sommer. Drugs that block EZH2 probably offer a promising strategy when it comes to treating melanoma, possibly in combination with immunotherapies, according to Sommer.

Source-Eurekalert

Novel Therapeutic Strategy to Treat Melanoma
Combination therapy co-targeting the mitochondria enhances the antitumor effect of telomerase inhibition in NRAS-mutant melanoma.