CeMM: How cancer becomes transmissible in Tasmanian devils: molecular mechanisms elucidated

Facial tumors of Tasmanian devils belong to the extremely rare cases of transmissible cancers. Nevertheless, they are highly interesting for biomedical research, as they allow the study of fundamental properties of cancer cells and their interaction with the host´s immune system. Scientists at CeMM, the Vienna University of Veterinary Medicine, the Medical University of Vienna and the LBI for Cancer Research were able to elucidate key molecular mechanisms that are crucial for the transmissibility of the tumor cells. The study „The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease” was published in Cancer Cell, on 14 January 2019, DOI: 10.1016/j.ccell.2018.11.018.

Tumors usually grow exclusively in the organism where their cell of origin derives from. The same applies for human cancers: apart from some rare cases, like the accidental transmission by a cut during surgery, there a no reports on contagious cancer cells. A multitude of molecular safety measures of the immune system is responsible for rejecting and destroying any foreign tissue.

An exception to this nearly universal rule exists among Tasmanian devils, the world’s largest living carnivorous marsupial. Since two decades, a deadly facial tumor is spreading at a rapid pace among the animals that killed according to current estimates around 90 percent of the wild population. Peculiarly, the cancer cells are transmitted from one Tasmanian devil to the other by bites. All collected tumor samples are genetically nearly identical and derive presumably from a single cell of origin.

How this cancer became transmissible and by what means it escapes the immune system of its otherwise healthy hosts puzzled scientists since the discovery of the mysterious disease. The scientists found that receptor molecules on the surface of the cancer cells, so-called ERBB receptors, show massively increased activity. Those receptors trigger a biochemical chain reaction within the cells that eventually activates STAT3 proteins, transcription factors that alter the cell’s genetic program. The result is an extensive rebuild of the cell: The number of molecules serving as identification for the immune system are reduced, while at the same time proliferation is accelerated and factors for metastasis of the tumor cells are produced.

Publication: Lindsay Kosack*, Bettina Wingelhofer*, Alexandra Popa*, Anna Orlova*, Benedikt Agerer, Bojan Vilagos, Peter Majek, Katja Parapatics, Alexander Lercher, Anna Ringler, Johanna Klughammer, Mark Smyth, Kseniya Khamina, Hatoon Baazim, Elvin D. de Araujo, David A. Rosa, Jisung Park, Gary Tin, Siawash Ahmar, Patrick T. Gunning, Christoph Bock, Hannah V. Siddle, Gregory M. Woods, Stefan Kubicek, Elisabeth P. Murchison, Keiryn L. Bennett, Richard Moriggl*, and Andreas Bergthaler*. The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor. Cancer Cell 35, 1-15 January 14, 2019. DOI: 10.1016/j.ccell.2018.11.018.*These authors contributed equally.

The study was funded by the Austrian Academy of Sciences, the Austrian Science Fund (FWF), the European Research Council (ERC) and the Austrian Research Promotion Agency (FFG).