Activated STAT regulates growth and induces competitive interactions independently of Myc, Yorkie, Wingless and ribosome biogenesis. Tamara Zoranovic¹, Aloma Rodrigues¹, Aidee Ayala-Camargo¹, Savraj Grewal², Tamara Reyes-Robles¹, Michelle Krasny¹, D. Christine Wu³, Laura Johnston³, Erika Bach¹. 1) Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA; 2) Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada; 3) Department of Genetics and Development, Columbia University, New York, NY, USA.

   Cell competition is a conserved mechanism that regulates organ size and shares properties with the early stages of cancer. In Drosophila, wing cells with increased Myc or with optimum ribosome function become supercompetitors that kill their wild-type neighbors (called losers) up to several cell diameters away (1,2). Here, we report that modulating STAT activity levels regulates competitor status. Cells lacking STAT become losers that are killed by neighboring wild-type cells. By contrast, cells with hyper-activated STAT become supercompetitors that kill losers located at a distance in a manner that is dependent on hid but independent of Myc, Yorkie (3-5), Wingless (6) signaling, and of ribosome biogenesis (7-9). These results indicate that STAT, Wingless and Myc are major parallel regulators of cell competition, which may converge on signals that non-autonomously kill losers. As hyper-activated STATs are causal to tumorigenesis and stem cell niche occupancy, our results have therapeutic implications for cancer and regenerative medicine.
    References cited: 1. de la Cova et al., Cell, 2004. 2. Moreno and Basler, Cell, 2004. 3. Tyler et al., Genetics, 2007. 4. Neto-Silva et al., Dev Cell, 2010. 5. Ziosi et al., PLoS Genetics, 2010. 6. Vincent et al., Dev Cell, 2011. 7. Morata and Ripoll, Dev Biol, 1975. 8. Simpson, Dev Biol, 1979. 9. Simpson and Morata, Dev Biol, 1981.
   This work was supported by Canadian Institutes of Health Research (to SG) and by the National Institutes of Health (to LAJ and to EAB).