Systematic identification of a nuclear receptor-enriched predictive signature for erastin-induced ferroptosis
- 주제(키워드) Aryl hydrocarbon receptor , Drug response biomarker , Drug sensitivity prediction , Elastic net , Erastin , Ferroptosis , NRF2 , Redox imbalance
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published, Green Submitted
- 발행기관 Elsevier B.V.
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000174710
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.redox.2020.101719
- PubMed https://pubmed.ncbi.nlm.nih.gov/32979793
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Erastin, a synthetic lethal compound against cancer expressing an oncogenic RAS, inhibits cystine/glutamate antiporters and causes ferroptosis. However, despite recent evidence for the mechanisms underlying ferroptosis, molecular biomarkers of erastin-dependent ferroptosis have not been identified. Here, we employed isogenic lung cancer cell models to show that a redox imbalance leads to glutathione depletion and ferroptosis. Subsequent transcriptome analysis of pan-cancer cell lines revealed that the activity of transcription factors, including NRF2 and AhR, serve as important markers of erastin resistance. Based on the integrated expression of genes in the nuclear receptor meta-pathway (NRM), we constructed an NRM model and validated its robustness using an independent pharmacogenomics dataset. The NRM model was further evaluated by sensitivity tests on nine cancer cell lines for which erastin sensitivities had not been determined. Our pharmacogenomics approach has the potential to pave the way for the efficient classification of patients for therapeutic intervention using erastin. © 2020 The Author(s)
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