American Association for Cancer Research
00085472can120371-sup-supplementary_online_material.pdf (195.9 kB)

Supplementary Methods and Materials from Targeting the EWSR1-FLI1 Oncogene-Induced Protein Kinase PKC-β Abolishes Ewing Sarcoma Growth

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journal contribution
posted on 2023-03-30, 21:04 authored by Didier Surdez, Magdalena Benetkiewicz, Virginie Perrin, Zhi-Yan Han, Gaëlle Pierron, Stelly Ballet, François Lamoureux, Françoise Rédini, Anne-Valérie Decouvelaere, Estelle Daudigeos-Dubus, Birgit Geoerger, Gonzague de Pinieux, Olivier Delattre, Franck Tirode

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