Pro-Tumorigenic role of ETS-related gene (ERG) in precursor prostate cancer lesions

Prostate cancer (PCa) is the second most common cancer in men with more than 1 million new cases worldwide each year. While some of the genomic, genetic and molecular events characterizing PCa have been functionally associated with tumor onset, development and resistance to therapy, the meaning of many other molecular alterations remains poorly understood. Recent development of organoids technology and prostate organoid cultures has established an innovative and valuable model for the study of adult tissue homeostasis, physiology and disease. In this project we combined prostate organoids technology with genetic engineering and CLICK-chemistry coupled Mass Spectrometry approaches in order to better characterize molecular features of wild type and genetically engineered mouse prostate organoids modeling early steps of human prostate tumorigenesis. In details, by manipulating mPrOs to proxy ETS-related gene (ERG) precursor PIN/HGPIN lesions of human prostate, we identified possible novel pro-tumorigenic roles of ERG which unleashes cells proliferation from the tight control of growth stimuli, and, even more interesting, corrupts immune system components to escape immune surveillance. In conclusion, this project shows that coupling innovative biological systems and technological approaches can lead to significant improvements in the analysis and understanding of disease mechanisms.