ArticleApoptosis : an international journal on programmed cell death2024
Targeting PAX8 sensitizes ovarian cancer cells to ferroptosis by inhibiting glutathione synthesis.
Article in Apoptosis : an international journal on programmed cell death, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Research progress of ferroptosis in gynecological diseases.Annals of medicine · 2026Review
- APOC1⁺IFI30⁺ TAMs orchestrate colorectal cancer liver metastasis by coupling cholesterol biosynthesis with secretion of immunosuppressive factors.Cellular and molecular life sciences : CMLS · 2026Article
- ZBTB7A promotes malignant phenotypes in ovarian cancer through transcriptional activation of CRLF1.Oncology reports · 2026Article
- CRISPR technology in ovarian cancer research: advances from gene editing to precision diagnosis and therapy.Translational cancer research · 2026Review
- LncRNA-PRLB drives ovarian cancer progression and chemoresistance by stabilizing GPX4 mRNA through the FUS-mediated suppression of ferroptosis.Frontiers in medicine · 2026Article
- Advances in ferroptosis research in ovarian cancer: molecular mechanisms and therapeutic perspectives.American journal of cancer research · 2026Review
- Regulated cell death in ovarian cancer: molecular mechanisms and therapeutic targets.Frontiers in cell and developmental biology · 2026Review
- Ferroptosis: A Double-Edged Sword in Cisplatin-Based Cancer Therapy and Acute Kidney Injury.Cancer management and research · 2026Review
- Crosstalk between microRNA and oxidative stress in ovarian cancer: diagnosis, pathogenesis and therapeutic resistance.Medical oncology (Northwood, London, England) · 2025Review
- Machine learning constructs a ferroptosis related signature for predicting prognosis and drug sensitivity in lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Revealing genetic drivers of ovarian cancer and chemoresistance: insights from whole-genome CRISPR-knockout library screens.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Ferroptosis in cancer: revealing the multifaceted functions of mitochondria.Cellular and molecular life sciences : CMLS · 2025Review
- Targeting Ferroptosis in Tumors: Novel Marine-Derived Compounds as Regulators of Lipid Peroxidation and GPX4 Signaling.Marine drugs · 2025Review
- Crosstalk between ferroptosis and endoplasmic reticulum stress: A potential target for ovarian cancer therapy (Review).International journal of molecular medicine · 2025Review
- A cellular danse macabre: the choreography of programmed cell death.Apoptosis : an international journal on programmed cell death · 2025Article
- Targeting ferroptosis: a promising avenue for ovarian cancer treatment.Frontiers in immunology · 2025Review
- Review
- Ferroptosis: mechanism, immunotherapy and role in ovarian cancer.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ovarian cancer is a malignant tumor originating from the ovary, characterized by its high mortality rate and propensity for recurrence. In some patients, especially those with recurrent cancer, conventional treatments such as surgical resection or standard chemotherapy yield suboptimal results. Consequently, there is an urgent need for novel anti-cancer therapeutic strategies. Ferroptosis is a distinct form of cell death separate from apoptosis. Ferroptosis inducers have demonstrated promising potential in the treatment of ovarian cancer, with evidence indicating their ability to enhance ovarian cancer cell sensitivity to cisplatin. However, resistance of cancer cells to ferroptosis still remains an inevitable challenge. Here, we analyzed genome-scale CRISPR-Cas9 loss-of function screens and identified PAX8 as a ferroptosis resistance protein in ovarian cancer. We identified PAX8 as a susceptibility gene in GPX4-dependent ovarian cancer. Depletion of PAX8 rendered GPX4-dependent ovarian cancer cells significantly more sensitive to GPX4 inhibitors. Additionally, we found that PAX8 inhibited ferroptosis in ovarian cancer cells. Combined treatment with a PAX8 inhibitor and RSL3 suppressed ovarian cancer cell growth, induced ferroptosis, and was validated in a xenograft mouse model. Further exploration of the molecular mechanisms underlying PAX8 inhibition of ferroptosis mutations revealed upregulation of glutamate-cysteine ligase catalytic subunit (GCLC) expression. GCLC mediated the ferroptosis resistance induced by PAX8 in ovarian cancer. In conclusion, our study underscores the pivotal role of PAX8 as a therapeutic target in GPX4-dependent ovarian cancer. The combination of PAX8 inhibitors such as losartan and captopril with ferroptosis inducers represents a promising new approach for ovarian cancer therapy.
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