Epigenetic Control Protein Allows Melanoma Cells To Metatasize

MedicalResearch.com Interview with:
Prof Lukas Sommer. Ph.D.
Cell and Developmental Biology
University of Zurich Institute of Anatomy
Zurich Switzerland

MedicalResearch: What is the background for this study? What are the main findings?

Prof. Lukas Sommer:   Melanoma, the most aggressive of all skin cancers, is often fatal for patients due to the pronounced formation of metastases. Up to date, a melanoma’s rampant growth was mainly attributed to genetic causes, such as mutations in certain genes. However, we now reveal that so-called epigenetic factors also play a crucial role in the formation of metastases in malignant skin cancer. Epigenetic factors 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. In our study we identified “EZH2” as an epigenetic control protein found very frequently in malignant melanoma cells compared to normal cells. In these cells, “EZH2” controls genes that govern both tumor growth and genes that are important for the formation of metastases. We exploited this central position of EZH2 to combat the cancer by using a pharmacological inhibitor to suppress the activity of EZH2. As a result, we were able to prevent the growth and malignant spread of the cancer in an animal model and in human melanoma cells.

MedicalResearch: What should clinicians and patients take away from your report?

Prof. Lukas Sommer: Various cancer drugs have been developed that target signaling pathways activated by genetic alterations in tumor cells. Some of these drugs 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. We believe that, depending on the prevalent conditions, cancer cells are able to “read” different genes and use them to their own end. Epigenetic control mechanisms such as the one identified in our study are likely key players in this process. Thus, combinatorial treatments that include targeting of epigenetic control proteins such as “EZH2” might open up new possibilities for future cancer treatments.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Prof. Lukas Sommer:   An imminent research question arising from our study is whether development of resistance to currently used anti-cancer drugs in melanoma indeed involves epigenetic regulation. Could we prevent cancer cells from using alternative ways to grow by blocking epigenetic factors such as “EZH2”? This remains to be shown in future studies.

Citation:

The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors

Nat Commun. 2015 Jan 22;6:6051. doi: 10.1038/ncomms7051.

Zingg D1, Debbache J1, Schaefer SM1, Tuncer E1, Frommel SC2, Cheng P3, Arenas-Ramirez N4, Haeusel J1, Zhang Y1, Bonalli M1, McCabe MT5, Creasy CL5, Levesque MP3, Boyman O4, Santoro R2, Shakhova O6, Dummer R3, Sommer L1.