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Study Reveals Restricting Cilia Formation Develops Aggressive Melanoma

Researchers from University of Zurich reveal that fine sensory antennae play a vital role in the formation of melanoma.

Cilium is a slender cell protuberance that picks up signals from the cell’s external environment. Majority of human cells contain this slender cell protuberance. Now researchers from University of Zurich suggest that these fine cilium plays a key role in the formation of melanoma. Restraining development of cilia in benign pigment cells leads to cell degeneration, eventually developing an aggressive form of melanoma in humans.  Despite immunotherapies, it is observed that there are still many melanoma patients awaiting efficient cure. These patients often suffer a recurrence of the disease following immunotherapies in later years. The research led by Lukas Sommer, professor at the Institute of Anatomy at UHZ began with an aim to understand the tumor’s biology that can boost novel therapeutic approaches. The team revealed that along with genetic causes such as mutations in the DNA, epigenetic factors are highly responsible for formation and spread of melanoma. Although epigenetic factors do not directly influence the gene sequence, they affected the extent of certain gene transcription in the cells. The EZH2 protein hardly found in benign cells was evident in melanoma cells and extensively affected melanoma formation. The research was published in the online journal Cell Cancer on June 28, 2018.

The team analyzed several genes associated to EZH2 to establish a link between melanoma’s aggressive behavior and its epigenetic factors. The results reveled that many genes were jointly responsible for the formation of cilia. It was observed that cilia genes are suppressed by EZH2 leading to much fewer fine sensory hairs in malignant melanoma cells compared to the skin’s benign pigment cells. Human melanoma cells and mouse models aided to demonstrate that the loss of cilia in pigment cells activates carcinogenic signaling pathways, which in turn forms aggressive metastatic melanoma. Several types of cancers consist of cells that lose their cilia. Hence, such epigenetic regulation might be evident in other types of cancers, such as breast or brain tumors. These conclusions can help in development of better therapies to block EZH2 and effectively treat melanoma.