Abstract
IntroductionThe EWS‐FLI1 oncogenic fusion protein is derived from a tumor‐specific t(11;22) chromosomal translocation that is uniquely expressed in Ewing's Sarcoma. We hypothesize that peptides interacting with EWS‐FLI1 can modulate protein function and improve therapies for Ewing's Sarcoma patients.MethodsPhage display peptide screening was performed by using EWS‐FLI1 as the bait.ResultsWe identified 27 unique EWS‐FLI1 binding peptides. These Ewing Sarcoma Antagonist peptides (ESAPs) were synthesized with Antennapedia and evaluated in TC32 (Ewing's Sarcoma), and SKNAS (neuroblastoma) cell lines for growth inhibition. We found that the cytotoxicity for ESAP‐1 is the most potent among other peptides. We further explored this peptide's inhibitory effect in Ewing's Sarcoma. We confirmed that ESAP‐1 peptide binds directly to EWS‐FLI1 by ELISA and Surface Plasmon Resonance. This peptide reduced the transcriptional activity of EWS‐FLI1 and interfered the cell cycle by G2M arrest.DiscussionThe ESAP‐1 peptide directly binds to the EWS‐FLI1 and leads to cell death in cells that harbor this fusion protein. This finding provides a novel experimental and potential therapeutic tool for Ewing's Sarcoma. This work is supported by Children's Cancer Foundation, Baltimore, MD
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