ArticleOncogene2024
NRF2 activation by cysteine as a survival mechanism for triple-negative breast cancer cells.
Article in Oncogene, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Evaluation of Curcumin as a Supplement to Improve Mitotane Effects on Adrenocortical Carcinoma.Cells · 2026Article
- Disulfidptosis and its molecular mechanisms in cancer: mechanisms, regulation, and therapeutic potential.Medical oncology (Northwood, London, England) · 2026Review
- Tipping the balance: NRF2's dual role in ferroptotic fate.Oncogenesis · 2026Review
- Redefining the role of the thiol-based agentRSC medicinal chemistry · 2026Review
- Whey Processed Oxymel induces apoptosis and S-phase arrest in MCF7 and MDA-MB-468 breast cancer cells.Scientific reports · 2026Article
- BioGate SERS Chip enables robust metabolite-oriented nanobiotechnological detection of breast cancer margins.Journal of nanobiotechnology · 2026Article
- Oxidative stress causes a reversible decrease of deubiquitylases activity in old vertebrate brains.Nature communications · 2026Article
- Regulation of mitochondrial ROS by C15ORF48 in a basal cell subpopulation contributes to chemotherapy resistance in TNBC.Science advances · 2026Article
- Targeting of a novel interplay between MET tyrosine kinase and NRF2 enhances sensitivity to Paclitaxel in triple negative breast cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Oxidative stress and antioxidants in breast cancer: a double-edged sword.Frontiers in oncology · 2026Review
- From metabolism to genome integrity: NRF2 as a key mediator of cancer therapy response.Frontiers in cell and developmental biology · 2026Review
- Dynamic Metabolic States in TNBC: Orchestrating Spatiotemporal Adaptation and Therapy.Oncology research · 2026Review
- The Central Role of NRF2 in Cancer Metabolism and Redox Signaling: Novel Insights into Crosstalk with ER Stress and Therapeutic Modulation.Cell biochemistry and biophysics · 2025Review
- N-acetyl-l-cysteine ethyl ester (NACET) induces the transcription factor NRF2 and prevents retinal aging and diabetic retinopathy.Redox biology · 2025Article
- Metabolic interplay between exogenous cystine and glutamine dependence in triple-negative breast cancer.Cell death discovery · 2025Article
- Ferroptosis and Metabolic Dysregulation: Emerging Chemical Targets in Cancer and Infection.Molecules (Basel, Switzerland) · 2025Review
- Silibinin Anticancer Effects Through the Modulation of the Tumor Immune Microenvironment in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- Interplay between Nrf2 and ROS in regulating epithelial-mesenchymal transition: implications for cancer metastasis and therapy.Molecular biology reports · 2025Review
- Unraveling the nexus: Genomic instability and metabolism in cancer.Cell reports · 2025Review
- Genome-wide association study identifies common variants associated with breast cancer in South African Black women.Nature communications · 2025Article
Corrections and comments
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triple-negative breast cancer (TNBC) is a very aggressive and heterogeneous group of tumors. In order to develop effective therapeutic strategies, it is therefore essential to identify the subtype-specific molecular mechanisms underlying disease progression and resistance to chemotherapy. TNBC cells are highly dependent on exogenous cystine, provided by overexpression of the cystine/glutamate antiporter SLC7A11/xCT, to fuel glutathione synthesis and promote an oxidative stress response consistent with their high metabolic demands. Here we show that TNBC cells of the mesenchymal stem-like subtype (MSL) utilize forced cystine uptake to induce activation of the transcription factor NRF2 and promote a glutathione-independent mechanism to defend against oxidative stress. Mechanistically, we demonstrate that NRF2 activation is mediated by direct cysteinylation of the inhibitor KEAP1. Furthermore, we show that cystine-mediated NRF2 activation induces the expression of important genes involved in oxidative stress response, but also in epithelial-to-mesenchymal transition and stem-like phenotype. Remarkably, in survival analysis, four upregulated genes (OSGIN1, RGS17, SRXN1, AKR1B10) are negative prognostic markers for TNBC. Finally, expression of exogenous OSGIN1, similarly to expression of exogenous NRF2, can prevent cystine depletion-dependent death of MSL TNBC cells. The results suggest that the cystine/NRF2/OSGIN1 axis is a potential target for effective treatment of MSL TNBCs.
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