ArticleThe Journal of clinical investigation2024
ZMYND8 protects breast cancer stem cells against oxidative stress and ferroptosis through activation of NRF2.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- The mechanism of breast cancer stem cells and tumor microenvironment promoting radioresistance in breast cancer and its intervention strategies.Frontiers in immunology · 2026Pooled it
- Integrated computational and in vitro investigation to explore the preliminary anti-proliferative and anti-mitotic potential of γ-oryzanol against breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- CRISPR/Cas9 screen identifies DCAF4 as a novel protector of hepatocellular carcinoma against brachytherapy via stress granule-dependent NRF2 activation.Cell death & disease · 2026Article
- Nrf2 signaling pathway and its molecular regulatory mechanism.Journal of Zhejiang University. Science. B · 2026Review
- The chromatin reader ZMYND8 recruits the NuRD component GATAD2A through its MYND domain to regulate MAPT213 long noncoding RNA transcription.The Journal of biological chemistry · 2026Article
- Article
- Ferroptosis in Breast Cancer: Molecular Insights and Therapeutic Strategies.Frontiers in bioscience (Landmark edition) · 2026Review
- POU1F1 induces cancer stem cell-like traits in breast cancer cells by IL-6/JAK2/STAT3 activation and enrichment of ALDH.NPJ breast cancer · 2026Article
- CPT1A as a metabolic gatekeeper linking fatty acid oxidation, ferroptosis resistance, and breast cancer stemness.Frontiers in oncology · 2026Review
- Article
- Polyphyllin B induces ferroptosis in triple-negative breast cancer by inactivating NRF2.Frontiers in pharmacology · 2026Article
- Transcription factor TFAP2A drives the growth and metastasis and blocks ferroptosis of triple-negative breast cancer by activating PRAME transcription.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Histone lysine demethylases in breast cancer: molecular mechanisms, biological functions, and therapeutic intervention.Molecular cancer · 2025Review
- Characterization of Differential GPX4 Essentiality Between Intrahepatic and Extrahepatic Cholangiocarcinoma via Leveraging of a Large-Scale Functional Genomic Screen.International journal of molecular sciences · 2025Article
- 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
- Epigenetic reprogramming as the nexus of cancer stemness and therapy resistance: implications for biomarker discovery.Discover oncology · 2025Review
- The dual impact of oxidative stress on breast cancer.Scientific reports · 2025Article
- Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment.Genes & diseases · 2025Review
- Deciphering the Role of Functional Ion Channels in Cancer Stem Cells (CSCs) and Their Therapeutic Implications.International journal of molecular sciences · 2025Review
- Epigenetic Mechanisms Governing Nrf2 Expression and Its Role in Ferroptosis.Biomedicines · 2025Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Breast cancer stem cells (BCSCs) mitigate oxidative stress to maintain their viability and plasticity. However, the regulatory mechanism of oxidative stress in BCSCs remains unclear. We recently found that the histone reader ZMYND8 was upregulated in BCSCs. Here, we showed that ZMYND8 reduced ROS and iron to inhibit ferroptosis in aldehyde dehydrogenase-high (ALDHhi) BCSCs, leading to BCSC expansion and tumor initiation in mice. The underlying mechanism involved a two-fold posttranslational regulation of nuclear factor erythroid 2-related factor 2 (NRF2). ZMYND8 increased stability of NRF2 protein through KEAP1 silencing. On the other hand, ZMYND8 interacted with and recruited NRF2 to the promoters of antioxidant genes to enhance gene transcription in mammospheres. NRF2 phenocopied ZMYND8 to enhance BCSC stemness and tumor initiation by inhibiting ROS and ferroptosis. Loss of NRF2 counteracted ZMYND8's effects on antioxidant genes and ROS in mammospheres. Interestingly, ZMYND8 expression was directly controlled by NRF2 in mammospheres. Collectively, these findings uncover a positive feedback loop that amplifies the antioxidant defense mechanism sustaining BCSC survival and stemness.
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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.