Suppression of ABCE1-Mediated mRNA Translation Limits N-MYC-Driven Cancer Progression
Jixuan Gao, MoonSun Jung, Chelsea Mayoh, Pooja Venkat, Katherine M Hannan, Jamie Fletcher, Alvin Kamili, Andrew J Gifford, Eric P Kusnadi, Richard B Pearson, Ross D Hannan, Michelle Haber, Murray D Norris, Klaartje Somers, Michelle J Henderson
CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2020
The ability of the N-MYC transcription factor to drive cancer progression is well demonstrated in neuroblastoma, the most common extracranial pediatric solid tumor, where MYCN amplification heralds a poor prognosis, with only 11% of high-risk patients surviving past 5 years. However, decades of attempts of direct inhibition of N-MYC or its paralogues has led to the conclusion that this protein is "undruggable." Therefore, targeting pathways upregulated by N-MYC signaling presents an alternative therapeutic approach. Here, we show that MYCN-amplified neuroblastomas are characterized by elevated rates of protein synthesis and that high expression of ABCE1, a translation factor directly upregul..View full abstract
Awarded by National Health and Medical Research Council
Awarded by Cancer Institute NSW
Awarded by Tour de Cure
We acknowledge Dr. Jayne Murray, Dr. Emanuele Valli, Dr. Denise Yu, Dr. Tzong-Tyng Hung, Dr. Brendan Lee, Mr. Janith Seneviratne, Miss Lara Martin, and Miss Ashley Weir for their technical advice or help with performing certain experiments. We would like to thank Drs. Charles De Bock and Tao Liu for their review of the article. This work was supported by the National Health and Medical Research Council (APP1016699 and APP1132608 to M. Haber and M.D. Norris), Cancer Institute NSW (10/TPG/1-03 and 14/TPG/1-13 to M. Haber and M.D. Norris), Tour de Cure (RG162423 to M.J. Henderson), the Australian Postgraduate Award (to J. Gao), and Children's Cancer Institute and Cancer Therapeutics CRC PhD Top-up Scholarship (to J. Gao).