ArticleCell death & disease2024
Iron promotes ovarian cancer malignancy and advances platinum resistance by enhancing DNA repair via FTH1/FTL/POLQ/RAD51 axis.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- From Iron to Depression: The Crosstalk Between the Periphery and Brain.Neuroscience bulletin · 2026Review
- Acetylation in ovarian cancer: mechanistic insights into drug resistance and emerging therapeutic opportunities.Journal of ovarian research · 2026Review
- Pyroptosis- and Necroptosis-Related Signaling in Salicylate UV Absorber-Induced Toxicity: Implications for Sustainable Chemistry and Human Health.International journal of molecular sciences · 2026Article
- Dissecting origin factors of lymph node metastasis in non-small cell lung cancer via multimodal omics.Nature communications · 2026Article
- RAD51 promotes osteogenic differentiation and inhibits DNA damage in osteoporosis though regulating cGAS-STING signaling pathway.Regenerative therapy · 2026Article
- HiST: Histological Images Reconstruct Tumor Spatial Transcriptomics via MultiScale Fusion Deep Learning.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Iron and metabolic rewiring in cancer.Oncogenesis · 2026Review
- IPO9 Promotes Ovarian Cancer Progression by Suppressing HMOX1-Dependent Ferroptosis.Human mutation · 2026Article
- Translational Aspects of DNA Damage Repair in Optimizing Cancer Chemotherapy.Advanced genetics (Hoboken, N.J.) · 2025Review
- Exploiting dysregulated iron homeostasis to eradicate persistent high-grade serous ovarian cancer.Cell death discovery · 2025Article
- HIF-1α alleviates ferroptosis in ulcerative colitis by regulation of GPX4.Cell death & disease · 2025Article
- CD36 promotes iron accumulation and dysfunction in CD8+ T cells via the p38-CEBPB-TfR1 axis in early-stage hepatocellular carcinoma.Clinical and molecular hepatology · 2025Article
- UVB irradiation induces melanocyte damage through ferroptosis: mechanisms and implications.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2025Article
- Lactoferrin-A Regulator of Iron Homeostasis and Its Implications in Cancer.Molecules (Basel, Switzerland) · 2025Review
- High taurocholic acid concentration induces ferroptosis by downregulating FTH1 expression in intrahepatic cholestasis of pregnancy.BMC pregnancy and childbirth · 2025Article
- The relationship between whole blood iron and fasting blood glucose in community-dwelling elderly people: a cross-sectional study.Journal of health, population, and nutrition · 2025Article
- Transferrin receptor uptakes iron from tumor-associated neutrophils to regulate invasion patterns of OSCC.Cancer immunology, immunotherapy : CII · 2025Article
- Deubiquitinating enzymes: Key regulators of ferroptosis and pyroptosis and novel targets for cancer intervention.International journal of biological sciences · 2025Review
- Review
- Iron overload promotes myeloid differentiation of normal hematopoietic stem cells and educates macrophage mediated immunosuppression in acute myeloid leukemia.Frontiers in immunology · 2025Article
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Authors and funding
7 authors.
Funding
Abstract
Iron is crucial for cell DNA synthesis and repair, but an excess of free iron can lead to oxidative stress and subsequent cell death. Although several studies suggest that cancer cells display characteristics of 'Iron addiction', an ongoing debate surrounds the question of whether iron can influence the malignant properties of ovarian cancer. In the current study, we initially found iron levels increase during spheroid formation. Furthermore, iron supplementation can promote cancer cell survival, cancer spheroid growth, and migration; vice versa, iron chelators inhibit this process. Notably, iron reduces the sensitivity of ovarian cancer cells to platinum as well. Mechanistically, iron downregulates DNA homologous recombination (HR) inhibitor polymerase theta (POLQ) and relieves its antagonism against the HR repair enzyme RAD51, thereby promoting DNA damage repair to resist chemotherapy-induced damage. Additionally, iron tightly regulated by ferritin (FTH1/FTL) which is indispensable for iron-triggered DNA repair. Finally, we discovered that iron chelators combined with platinum exhibit a synergistic inhibitory effect on ovarian cancer in vitro and in vivo. Our findings affirm the pro-cancer role of iron in ovarian cancer and reveal that iron advances platinum resistance by promoting DNA damage repair through FTH1/FTL/POLQ/RAD51 pathway. Our findings highlight the significance of iron depletion therapy, revealing a promising avenue for advancing ovarian cancer treatment.
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