ArticleAntioxidants (Basel, Switzerland)2021
xCT-Driven Expression of GPX4 Determines Sensitivity of Breast Cancer Cells to Ferroptosis Inducers.
Article in Antioxidants (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 105 citations in OpenAlex.
- Article
- Polyethylene glycol-liposomal doxorubicin triggers ferroptosis in breast cancer through the KEAP1/NRF2 signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Metabolic pathways and cell death modalities in diabetic complications: unraveling pyroptosis, ferroptosis, cuproptosis, and disulfidptosis.Cell death discovery · 2026Review
- Review
- Ferroptosis in Vascular Diseases: A Mechanistic and Immunological Perspective on Therapeutic Targeting.Antioxidants (Basel, Switzerland) · 2026Review
- Therapy as a State-Generator: Dynamic Phenotypic Landscapes and Adaptive Stress Circuits in Chemotherapy Resistance of Breast Cancer.Antioxidants (Basel, Switzerland) · 2026Review
- Systematic Evaluation Defines the Limits of Ferroptosis in Cancer Therapy.bioRxiv : the preprint server for biology · 2026Article
- The Role of Se-Containing Glutathione Peroxidases and Thioredoxin Reductases in Oncogenesis: Expression Paradoxes and Therapeutic Prospects.Antioxidants (Basel, Switzerland) · 2026Review
- Ferroptosis and Cuproptosis in Cancer and Neurodegeneration: A Comprehensive Review of Modulation by Iron and Copper Chelators and Related Agents.Biomolecules · 2026Review
- Lipid Metabolism and Ferroptosis Resistance in Dormant Breast Cancer Cells: Emerging Therapeutic Vulnerabilities.Diagnostics (Basel, Switzerland) · 2026Review
- Ferroptosis as a Novel Therapeutic Strategy to Overcome Multidrug Resistance in Colorectal Cancer.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Orphan G protein-coupled receptor GPR137 regulates ferroptosis by targeting the Wnt/β-catenin pathway in sonic hedgehog-medulloblastoma.Translational cancer research · 2026Article
- Formononetin alleviated cisplatin-induced acute kidney injury by orchestrating renal tubular cell ferroptosis via PI3K/AKT/NRF2 pathway.Frontiers in pharmacology · 2026Article
- NCOA4-mediated ferroptosis conducive to EMT inhibition in colorectal cancer cells was achieved through the PI3K/AKT/mTOR pathway.Scientific reports · 2025Article
- Metabolic Regulation of Ferroptosis in Breast Cancer.International journal of molecular sciences · 2025Review
- P23 acts as a negative regulator of ferroptosis in NSCLC by blocking GPX4 degradation via chaperone-mediated autophagy.Molecular cancer · 2025Article
- Iron metabolism dysregulation and ferroptosis: Emerging drivers in pulmonary fibrosis pathogenesis and therapy.Molecules and cells · 2025Review
- High-intensity interval training attenuates cardiac injury by targeting ferroptosis and endoplasmic reticulum-stress in male rats with heart failure.Physiological reports · 2025Article
- Green tea enriched with catechins prevents particulate matterFood science and biotechnology · 2025Article
- Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Inducers of ferroptosis such as the glutathione depleting agent Erastin and the GPX4 inhibitor Rsl-3 are being actively explored as potential therapeutics in various cancers, but the factors that determine their sensitivity are poorly understood. Here, we show that expression levels of both subunits of the cystine/glutamate antiporter xCT determine the expression of GPX4 in breast cancer, and that upregulation of the xCT/selenocysteine biosynthesis/GPX4 production axis paradoxically renders the cancer cells more sensitive to certain types of ferroptotic stimuli. We find that GPX4 is strongly upregulated in a subset of breast cancer tissues compared to matched normal samples, and that this is tightly correlated with the increased expression of the xCT subunits SLC7A11 and SLC3A2. Erastin depletes levels of the antioxidant selenoproteins GPX4 and GPX1 in breast cancer cells by inhibiting xCT-dependent extracellular reduction which is required for selenium uptake and selenocysteine biosynthesis. Unexpectedly, while breast cancer cells are resistant compared to nontransformed cells against oxidative stress inducing drugs, at the same time they are hypersensitive to lipid peroxidation and ferroptosis induced by Erastin or Rsl-3, indicating that they are 'addicted' to the xCT/GPX4 axis. Our findings provide a strategic basis for targeting the anti-ferroptotic machinery of breast cancer cells depending on their xCT status, which can be further explored.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.