MedUni Vienna: Prostate cancer: Protein identified to reduce tumour growth

As prostate cancer progresses, it becomes increasingly aggressive and can metastasise. In this form, the tumour is difficult to treat, which is reflected in high mortality rates: Worldwide, the malignant disease of the prostate is the second most common cause of cancer death in men. An international study led by Lukas Kenner (MedUni Vienna) and Sabine Lagger (Vetmeduni Vienna) has now identified a protein that could slow tumour growth. The results, which have just been published in the top journal "Molecular Cancer", provide a new starting point for the development of therapies.

The complex molecular processes that lead to the progression of prostate cancer have not yet been fully clarified by science. The protein known as JUN is being intensively researched as a possible driver of tumour growth. "Numerous studies have shown that JUN is produced excessively in cancer. So, a link has been established between tumour growth and high JUN levels," says Lukas Kenner (Clinical Institute of Laboratory Medicine at MedUni Vienna, Department of Laboratory Animal Pathology at Vetmeduni Vienna), explaining the background to the current study. In collaboration with national and international partners, it was shown that the opposite is the case with prostate cancer: the research team's investigations using a mouse model and clinical samples revealed that the progression of prostate cancer is not accelerated but slowed down when JUN is present in high levels. On the contrary, it was observed that the tumour grows faster when the protein is missing.

The fact that JUN plays an important role in the activation of genes and various processes such as cell growth was discovered back in the 1980s. "In our investigations, we found that JUN is significantly involved in the regulation of prostate cancer by influencing the body's immune response," says Sabine Lagger from the Department of Laboratory Animal Pathology at Vetmeduni Vienna, explaining the connections currently being researched. If the protein is missing, the recruitment of certain immune cells in the tumour's micro-environment is impaired, which leads to accelerated cancer growth. These results could explain why Prostate cancer is less responsive to immune therapy and could help to understand how to reactivate local immune responses.

Most common cancer in men

Prostate cancer has been the most common cancer in men in Austria for decades. Every year, around 6,000 new cases and 1,300 deaths are registered as a result of prostate cancer. In the vast majority of cases, tumours in the prostate gland remain localised and are therefore easily treatable. However, around 20 per cent of patients develop metastatic prostate cancer, which remains difficult to treat. "Our research suggests that activating JUN could potentially be a promising therapeutic option for slowing the progression of prostate cancer," Sabine Lagger and Lukas Kenner summarise the significance of their study ahead of further investigations to confirm the results.

Publication: Molecular Cancer

JUN mediates the senescence associated secretory phenotype and immune cell recruitment to prevent prostate cancer progression;
Torben Redmer*, Martin Raigel*, Christina Sternberg*, Roman Ziegler, Clara Probst, Desiree Lindner, Astrid Aufinger, Tanja Limberger, Karolina Trachtova, Petra Kodajova, Sandra Högler, Michaela Schlederer, Stefan Stoiber, Monika Oberhuber, Marco Bolis, Heidi A. Neubauer, Sara Miranda, Martina Tomberger, Nora S. Harbusch, Ines Garces de los Fayos Alonso, Felix Sternberg, Richard Moriggl, Jean-Philippe Theurillat, Boris Tichy, Vojtech Bystry, Jenny L. Persson, Stephan Mathas, Fritz Aberger, Birgit Strobl, Sarka Pospisilova, Olaf Merkel, Gerda Egger, Sabine Lagger* & Lukas Kenner*
*shared contribution

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