ArticleJCI insight2024
4EBP1-mediated SLC7A11 protein synthesis restrains ferroptosis triggered by MEK inhibitors in advanced ovarian cancer.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Mitochondrial dysfunction-ferroptosis crosstalk drives renal fibrosis in chronic kidney disease.Renal failure · 2026Review
- Research progress of ferroptosis in gynecological diseases.Annals of medicine · 2026Review
- Gut-Liver Translocation of Bacteroides Uniformis Alleviates Advanced Metabolic Dysfunction-Associated Steatotic Liver Disease by Suppressing Hepatocyte Ferroptosis via Propionic Acid Secretion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Solute Carrier transporters in tumor metabolism and immune modulation: implications for therapy.Journal of translational medicine · 2026Review
- Targeting ferroptosis in cancer: from mechanistic insights to therapeutic approaches.Molecular biomedicine · 2026Review
- Active Components ofAntioxidants (Basel, Switzerland) · 2026Article
- Review
- Advances in ferroptosis research in ovarian cancer: molecular mechanisms and therapeutic perspectives.American journal of cancer research · 2026Review
- Modeling ovarian cancer chemoresistance: establishment of murine ID8 sublines and elucidation of adaptive mechanisms.Frontiers in oncology · 2026Article
- Targeting STK17B kinase activates ferroptosis and suppresses drug resistance in multiple myeloma.Blood · 2026Article
- Targeting Ferroptosis to Overcome Drug Resistance in Cancer: Molecular Mechanisms and Therapeutic Prospects.Biomolecules & therapeutics · 2026Review
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- USP26-mediated stabilization of RAD51 promotes endometrial cancer progression and limits ferroptosis.Frontiers in oncology · 2026Article
- 4EBP1 phosphorylation mediates TGF-β1-induced hepatic fibrosis and upregulates HIF-1α expression.iScience · 2025Article
- WDFY4 Promotes the Progression of Atherosclerosis by Regulating Ferroptosis Mediated by the LAPTM5/CDC42/mTOR/4EBP1/SLC7A11 Pathway.Journal of cellular and molecular medicine · 2025Article
- Whey Protein Mitigates Oxidative Stress Injury and Improves Protein Synthesis in Mouse Skeletal Muscle by Regulating the SIRT1/Nrf2/HO-1 Axis and AMPK/TSC2/mTOR/4EBP1 Pathway.Journal of food science · 2025Article
- Ferroptosis as a therapeutic vulnerability in MDM2 inhibition in dedifferentiated liposarcoma.Oncology letters · 2025Article
- Advances in Ferroptosis Research: A Comprehensive Review of Mechanism Exploration, Drug Development, and Disease Treatment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- eIF4F-mediated dysregulation of mRNA translation in cancer.RNA (New York, N.Y.) · 2025Review
- The dual role of SLC7A11 in tumor drug resistance: mechanisms, challenges, and therapeutic potential.American journal of cancer research · 2025Review
Corrections and comments
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Authors and funding
21 authors.
Funding
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Abstract
Loss of ferroptosis contributes to the development of human cancer, and restoration of ferroptosis has been demonstrated as a potential therapeutic strategy in cancer treatment. However, the mechanisms of how ferroptosis escape contributes to ovarian cancer (OV) development are not well elucidated. Here, we show that ferroptosis negative regulation signatures correlated with the tumorigenesis of OV and were associated with poor prognosis, suggesting that restoration of ferroptosis represents a potential therapeutic strategy in OV. High-throughput drug screening with a kinase inhibitor library identified MEK inhibitors as ferroptosis inducers in OV cells. We further demonstrated that MEK inhibitor-resistant OV cells were less vulnerable to trametinib-induced ferroptosis. Mechanistically, mTOR/eIF4E binding protein 1 (4EBP1) signaling promoted solute carrier family 7 member 11 (SLC7A11) protein synthesis, leading to ferroptosis inhibition in MEK inhibitor-resistant cells. Dual inhibition of MEK and mTOR/4EBP1 signaling restrained the protein synthesis of SLC7A11 via suppression of the mTOR/4EBP1 axis to reactivate ferroptosis in resistant cells. Together, these findings provide a promising therapeutic option for OV treatment through ferroptosis restoration by the combined inhibition of MEK and mTOR/4EBP1 pathways.
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