Targeting the EWSR1-FLI1 Oncogene-Induced Protein Kinase PKC-β Abolishes Ewing Sarcoma Growth

摘要: Ewing sarcoma is a rare but aggressive disease most common in young adults. This cancer driven by unique chimeric fusion oncogene targeted strategies have been elusive. Here we report the identification of protein kinase PKC-s (PRKCB) as disease-specific druggable target for treatment sarcoma. We found that transcriptional activation PRKCB was directly regulated EWSR1-FLI1 drives this cancer. phosphorylated histone H3T6 to permit global maintenance H3K4 trimethylation at variety gene promoters. loss induced apoptosis vitro and prevented tumor growth vivo . Gene expression profiling revealed strong overlap between genes modulated regulating crucial signaling pathways. Taken together, our findings offer preclinical proof-of-concept promising therapeutic Cancer Res; 72(17); 4494–503. ©2012 AACR