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A 12 Amino Acid Peptide Reduces the Oncogenic Potential of EWS‐FLI1 in Ewing's Sarcoma
Author(s) -
Erkizan Hayriye Verda,
JacobwitzScher Lauren M,
Gamble Ellen,
BarberRotenberg Julie,
Sajwan Kamal,
Uren Aykut,
Toretsky Jeffrey A
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb112
Subject(s) - fli1 , peptide , sarcoma , cancer research , ewing's sarcoma , fusion protein , chemistry , biology , microbiology and biotechnology , chromosomal translocation , medicine , biochemistry , gene , pathology , recombinant dna
The 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. Methods Phage display peptide screening was performed by using EWS‐FLI1 as the bait. Results We 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. Discussion The 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