idw – Informationsdienst Wissenschaft
Nachrichten, Termine, Experten
Nachrichten, Termine, Experten
Most cells in the human body have a cilium, a slender cell protuberance that picks up signals from the cell’s external environment. Researchers at the University of Zurich have now shown that these fine sensory antennae play a key role in the formation of melanoma. When cilia are prevented from developing in benign pigment cells, the cells degenerate and develop an aggressive form of melanoma.
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.
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
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. With the help of human melanoma cells and mouse models, the researchers succeeded in demonstrating that loss of cilia in pigment cells activates carcinogenic signaling pathways, ultimately resulting in the formation of aggressive, metastatic melanoma.
Approach for novel tumor therapies
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.
Literature:
Daniel Zingg, Julien Debbache, Rodrigo Peña-Hernández, Ana T. Antunes, Simon M. Schaefer, Phil F. Cheng, Dario Zimmerli, Jessica Haeusel, Raquel R. Calçada, Eylul Tuncer, Yudong Zhang, Raphaël Bossart, Kwok-Kin Wong, Konrad Basler, Reinhard Dummer, Raffaella Santoro, Mitchell P. Levesque, and Lukas Sommer. EZH2-mediated primary cilium deconstruction drives metastatic melanoma formation. Cancer Cell, June 28, 2018. DOI: 10.1016/j.ccell.2018.06.001
http://www.media.uzh.ch/en/Press-Releases/2018/Melanoma.html
Pigment cells (blue/green) with cilium (light green with red base).
Daniel Zingg, Netherlands Cancer Institute
None
Criteria of this press release:
Journalists, Scientists and scholars
Biology, Medicine
transregional, national
Research results, Scientific Publications
English
Pigment cells (blue/green) with cilium (light green with red base).
Daniel Zingg, Netherlands Cancer Institute
None
You can combine search terms with and, or and/or not, e.g. Philo not logy.
You can use brackets to separate combinations from each other, e.g. (Philo not logy) or (Psycho and logy).
Coherent groups of words will be located as complete phrases if you put them into quotation marks, e.g. “Federal Republic of Germany”.
You can also use the advanced search without entering search terms. It will then follow the criteria you have selected (e.g. country or subject area).
If you have not selected any criteria in a given category, the entire category will be searched (e.g. all subject areas or all countries).
