STAT3 regulated ARF expression suppresses prostate cancer metastasis.

Prostate cancer (PCa) is the most prevalent cancer in men. Hyperactive STAT3 is thought to be oncogenic in PCa. However, targeting of the IL-6/STAT3 axis in PCa patients has failed to provide therapeutic benefit. Here we show that genetic inactivation of Stat3 or IL-6 signalling in a Pten-deficient PCa mouse model accelerates cancer progression leading to metastasis. Mechanistically, we identify p19(ARF) as a direct Stat3 target. Loss of Stat3 signalling disrupts the ARF-Mdm2-p53 tumour suppressor axis bypassing senescence. Strikingly, we also identify STAT3 and CDKN2A mutations in primary human PCa. STAT3 and CDKN2A deletions co-occurred with high frequency in PCa metastases. In accordance, loss of STAT3 and p14(ARF) expression in patient tumours correlates with increased risk of disease recurrence and metastatic PCa. Thus, STAT3 and ARF may be prognostic markers to stratify high from low risk PCa patients. Our findings challenge the current discussion on therapeutic benefit or risk of IL-6/STAT3 inhibition.Lukas Kenner and Jan Pencik are supported by FWF, P26011 and the Genome Research-Austria project “Inflammobiota” grants. Helmut Dolznig is supported by the Herzfelder Family Foundation and the Niederösterr. Forschungs-und Bildungsges.m.b.H (nfb). Richard Moriggl is supported by grant SFB-F2807 and SFB-F4707 from the Austrian Science Fund (FWF), Ali Moazzami is supported by Infrastructure for biosciences-Strategic fund, SciLifeLab and Formas, Zoran Culig is supported by FWF, P24428, Athena Chalaris and Stefan Rose-John are supported by the Deutsche Forschungsgemeinschaft (Grant SFB 877, Project A1and the Cluster of Excellence --“Inflammation at Interfaces”). Work of the Aberger lab was supported by the Austrian Science Fund FWF (Projects P25629 and W1213), the European FP7 Marie-Curie Initial Training Network HEALING and the priority program Biosciences and Health of the Paris-Lodron University of Salzburg. Valeria Poli is supported by the Italian Association for Cancer Research (AIRC, No IG13009). Richard Kennedy and Steven Walker are supported by the McClay Foundation and the Movember Centre of Excellence (PC-UK and Movember). Gerda Egger is supported by FWF, P27616. Tim Malcolm and Suzanne Turner are supported by Leukaemia and Lymphoma Research.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms873

Iberoamerican Reviews

Reseñas iberoamericanasIberoamerican Review

Sister republics: Power and law in revolutionary Europe

Biohakiranje je novi i široki pojam koji obuhvaća raznolike aktivnosti eksperimentiranja na živim bićima. Biohakiranjem u genetičkom inženjerstvu možemo smatrati različite eksperimente s genetičkim materijalom, koje najčešće izvode školovani stručnjaci i znanstvenici koji su napustili formalne znanstvene zajednice, ili to mogu biti i ljudi koji nisu educirani stručnjaci ili znanstvenici i koji se biohakiranjem bave iz hobija ili kako bi ostvarili svoje vlastite ideje u području biologije. Oni se često okupljaju u biohakerskim zajednicama, čiji cilj je smanjivanje razlika između znanstvenog svijeta i samog društva. Laboratoriji tih zajednica su mjesta gdje se zainteresirane osobe mogu upoznati s tehnikama i materijalima koji se mogu koristiti u istraživanju. Zainteresirani pojedinci putem interneta mogu naručiti sve potrebno kako bi mogli samostalno kod kuće izvoditi istraživanja. Brojni studenti se tijekom studiranja uključuju u istraživanja i projekte te čak natječu kroz natjecanje IGEM (engl. International Genetically Engineered Machines). Veliki broj ljudi može sudjelovati u različitim biohakerskim aktivnostima te time doprinijeti znanosti. Iako vođeno dobrom idejom, međutim, biohakiranje je povezano s nizom problema, otvara brojna pitanja i nekad se nalazi na granici ilegalnog djelovanja. Budući aktivnosti biohakera nisu obuhvaćene unutar formalnih znanstvenih okvira, te su bez nadzora i samim tim nesigurne zbog mogućih povezanih rizika i opasnosti, biohakiranje bi moglo doći u konflikt sa brojnim sigurnosnim zakonodavnim odredbama, te će zasigurno biti neophodno zakonski regulirati te aktivnosti, što su neke zemlje već i napravile.Biohacking is a new and broad term that includes a large array of different experiments on living organisms. By biohacking in genetic engineering, we consider various experiments with genetic material, most commonly performed by educated professionals and scientists who have left formal scientific communities, or that they may be people who are not educated experts or scientists and who practice biohacking as a hobby or to pursue their ideas in the field of biology. They often gather in biohacker communities, whose goal is to reduce the gap between the scientific world and the society itself. Community labs (biohacker spaces) are places where interested persons are being acquainted with the techniques and materials that can be used in research. Interested individuals can order required materials online to be able to conduct research independently at home. Numerous students take part in research and projects during their studies and even compete through the IGEM (International Genetically Engineered Machines) competition. A great number of people can participate in various biohacker activities and thus contribute to science. Although driven by a good idea, biohacking is associated with several problems which raises a variety of questions and is sometimes on the verge of illegal activity. Biohacker activities are unsupervised and not covered by formal scientific frameworks which results in them being associated with risks and dangers. Moreover, biohacking could conflict with several security legislation. In the future it will certainly be necessary to legally regulate these activities and some countries have already done so