Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Down but not out – Inhibited Tyk2 retains anti-cancer activity

11.09.2015

Tyk2 is a key component of the immune system and has an important role in the defence against infections and cancer. Recent studies, however, have established that Tyk2 is strongly activated in certain types of cancer and that inhibition of its enzymatic activity stops cancer cell growth. A team from the Vetmeduni Vienna has now presented the first evidence that enzymatically inactive Tyk2 retains anti-cancer activity of immune cells in mice. Thus, Tyk2-inhibiting drugs do not impair the immune system’s fight against cancer. The results were published in the journal Oncoimmunology.

Tyrosine kinase 2 (Tyk2) is an enzyme involved in intracellular signalling and has an important role in activating the immune system. But enzymatically active Tyk2 can also promote excessive immune reactions and growth of certain cancer types.

Since several years, scientists are developing substances to specifically inhibit the kinase activity of Tyk2 for the treatment of inflammatory diseases and for potential use in cancer therapy. However, complications may occur: Tyk2 crucially contributes to the maturation and activation of natural killer (NK) cells.

NK cells form part of the innate immune system and are the first defence against virus infections and cancer. They recognise cancer cells and produce a series of proteins capable of destroying them. Inhibition of Tyk2 could therefore also weaken NK cells and block an important front of the body’s own defence against cancer.

First evidence of kinase-independent functions of Tyk2 in a living organism

A team of researchers led by Birgit Strobl, Mathias Müller and Veronika Sexl from the Institute of Animal Breeding and Genetics and the Institute of Pharmacology and Toxicology at the Vetmeduni Vienna investigated cancer growth in Tyk2 gene-targeted mice.

Tyk2-deficient mice were not able to control cancer growth. NK cells of these animals exhibited incomplete maturation and were unable to destroy cancer cells. Surprisingly, in mice whose Tyk2 was present but enzymatically inactivated, cancer growth was strongly suppressed and NK cells retained their ability to kill the cancer cells.

Project leader Birgit Strobl explains: “Until now, it was unknown that Tyk2 has effects within the whole organism that do not depend on its enzymatic activities. Without its kinase activity, it still drives NK cell maturation and boosts their activity. Here lies the key for cancer medicine. Drugs that inhibit the kinase activity of Tyk2 – and there are currently several of them in the testing phase – do not hamper the immune system in its work. These drugs are therefore even more promising for cancer therapy than previously thought.”

Research into proteins involved in the JAK/STAT signal pathway

The research forms part of a Special Research Programme (SFB) funded by FWF, the Austrian Science Fund. SFB F28 “Jak-Stat Signalling: From Basics to Disease” (http://www.jak-stat.at) involves a consortium of Viennese researchers with the participation of an international scientific network and aims to understand the function of JAKs (Janus kinases) and STATs (Signal Transducers and Activators of Transcription) in the context of inflammation, infection and cancer.

Service:
The article “In vivo tumor surveillance by NK cells requires TYK2 but not TYK2 kinase activity”, by
Michaela Prchal-Murphy, Agnieszka Witalisz-Siepracka, Karoline T. Bednarik, Eva Maria Putz, Dagmar Gotthardt, Katrin Meissl, Veronika Sexl, Mathias Müller and Birgit Strobl was published in the journal OncoImmunology. DOI:10.1080/2162402X.2015.1047579
http://www.tandfonline.com/doi/full/10.1080/2162402X.2015.1047579

About the University of Veterinary Medicine, Vienna
The University of Veterinary Medicine, Vienna in Austria is one of the leading academic and research institutions in the field of Veterinary Sciences in Europe. About 1,300 employees and 2,300 students work on the campus in the north of Vienna which also houses five university clinics and various research sites. Outside of Vienna the university operates Teaching and Research Farms. http://www.vetmeduni.ac.at

Scientific Contact:
Prof. Mathias Müller
Institute of Animal Breeding and Genetics
University of Veterinary Medicine Vienna (Vetmeduni Vienna)
T +43 1 25077-5620
mathias.mueller@vetmeduni.ac.at

Released by:
Heike Hochhauser
Corporate Communications
University of Veterinary Medicine Vienna (Vetmeduni Vienna)
T +43 1 25077-1151
heike.hochhauser@vetmeduni.ac.at

Weitere Informationen:

http://www.vetmeduni.ac.at/en/infoservice/presseinformation/press-releases-2015/...

Heike Hochhauser | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>