Melanoma, the most aggressive of all skin cancer strains, is often fatal for patients due to the pronounced formation of metastases. Until now, a melanoma’s rampant growth was mainly attributed to genetic causes, such as mutations in certain genes.
However, researchers from the University of Zurich now reveal that so-called epigenetic factors play a role in the formation of metastases in malignant skin cancer. This opens up new possibilities for future cancer treatments.
Patients who visit the doctor because of malignant skin cancer often go too late – the aggressive cancer has already formed numerous metastases in their bodies. This rapid, malignant metastatic formation of melanoma, was previously put down to the high mutation rate that is characteristic of melanoma, i.e. genetic changes that stimulate the growth of cancer cells.
Various cancer drugs therefore target the signaling pathways activated in the process, some of which have recorded astonishingly positive results in the clinic and are able to prolong the lives of seriously sick patients. Unfortunately, however, in most cases a kind of resistance develops: Eventually, the cancer cells no longer respond to the drug and the tumor spreads again.
Evidently, the cancer cells have found new ways to grow. A team of researchers headed by Professor Lukas Sommer from the University of Zurich’s Institute of Anatomy has now found a possible explanation for this dynamic behavior in cancer cells: The scientists believe that, depending on the prevalent conditions, cancer cells are able to “read” different genes and use them to their own end.
A highly active epigenetic factor in cancer cells
The readability of genes is controlled by epigenetic factors, namely factors which do not influence the gene sequence directly, but rather cause certain genes and chromosomal segments to be packed in different densities – and thus make them accessible for reading. Consequently, the Zurich-based researchers studied whether epigenetic factors are especially active in melanoma cells – and stumbled across EZH2, an epigenetic control protein found very frequently in malignant melanoma cells compared to normal cells.
Joining forces with dermatologists and oncologists from the University Hospital in Zurich and backed by the University Research Priority Program “Translational Cancer Research”, Sommer’s team was able to demonstrate that, in melanoma cells, the epigenetic factor EZH2 controls genes that govern tumor growth as well as genes that are important for the formation of metastases.
In their study, the researcher exploited this central position of EZH2 to combat the cancer: They used a pharmacological inhibitor to suppress the activity of EZH2. As a result, the researchers were able to prevent the growth and malignant spread of the cancer in the animal model and human melanoma cells.
“To our astonishment, we were able to use the approach to influence the progression of the disease, even if tumors had already developed,” explains Sommer. Epigenetic factors like EZH2 therefore appear to be highly promising targets for future cancer treatments, especially combined with other drugs that are already available.
Daniel Zingg, Julien Debbache, Simon M. Schaefer, Eylul Tuncer, Sandra C. Frommel, Phil Cheng, Natalia Arenas-Ramirez, Jessica Haeusel, Yudong Zhang, Michael T. McCabe, Caretha L. Creasy, Mitchell P. Levesque, Onur Boyman, Raffaella Santoro, Olga Shakhova, Reinhard Dummer, and Lukas Sommer. The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors. Nature Communications, 22 January, 2015. Doi: NCOMMS7051
Prof. Lukas Sommer
Institute of Anatomy
University of Zurich
Tel.: +41 44 635 53 50
University of Zurich
Tel.: +41 44 634 44 39
Bettina Jakob | Universität Zürich
The genes are not to blame
20.07.2018 | Technische Universität München
Targeting headaches and tumors with nano-submarines
20.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences