ArticleCell death & disease2018
High NRF2 level mediates cancer stem cell-like properties of aldehyde dehydrogenase (ALDH)-high ovarian cancer cells: inhibitory role of all-trans retinoic acid in ALDH/NRF2 signaling.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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76 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.
- Meta analysis of bioactive compounds, miRNA, siRNA and cell death regulators as sensitizers to doxorubicin induced chemoresistance.Apoptosis : an international journal on programmed cell death · 2022Pooled it
- Machine Learning-Guided Multi-Cohort Transcriptomic Profiling IdentifiesInternational journal of molecular sciences · 2026Article
- The metabolic profiles of cancer stem cells.Stem cell research & therapy · 2026Review
- Pleiotropic effects of all-trans retinoic acid in attenuating the hallmarks of colorectal cancer- challenges and scope of differentiation therapy.Cancer gene therapy · 2026Review
- Ovarian Cancer Stem Cells: Mechanisms of Progression and Therapeutic Strategies.Oncology research · 2026Review
- Imaging Sensing of Cadmium-Induced Single Cancer Stem Cells in Tumor Spheroid Fabricated by 3D Bioprinting.ACS applied materials & interfaces · 2025Article
- Pulsatile sequential drug release system for cascade tumor deep penetration and differentiation therapy to enhance chemoimmunotherapy.Science advances · 2025Article
- Tailoring a novel colorectal cancer stem cell-targeted therapy by inhibiting the SMYD3/c-MYC axis.Signal transduction and targeted therapy · 2025Article
- ALDH1A1 in breast cancer: A prospective target to overcome therapy resistance (Review).Oncology letters · 2025Review
- Drug combination discovery assisted by AI and untargeted metabolomics: pamiparib and anlotinib synergistic potentiation for ovarian cancer treatment.Frontiers in pharmacology · 2025Article
- The implication of aberrant NRF2 activation in management of female cancers.Frontiers in oncology · 2025Review
- Selenium enrichment enhances the alleviating effect ofCurrent research in food science · 2025Article
- Potential of NRF2 Inhibitors-Retinoic Acid, K67, and ML-385-In Overcoming Doxorubicin Resistance in Promyelocytic Leukemia Cells.International journal of molecular sciences · 2024Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Selected markers of ovarian cancer and their relation to targeted therapy (Review).Experimental and therapeutic medicine · 2024Review
- Identification of a set of genes potentially responsible for resistance to ferroptosis in lung adenocarcinoma cancer stem cells.Cell death & disease · 2024Article
- Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer.Experimental & molecular medicine · 2024Review
- Advances in the role of GPX3 in ovarian cancer (Review).International journal of oncology · 2024Article
- Biology-driven therapy advances in high-grade serous ovarian cancer.The Journal of clinical investigation · 2024Review
- Glucose metabolism reprogramming in gynecologic malignant tumors.Journal of Cancer · 2024Review
16 more citing papers are in PubMed but not listed here.
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4 authors at 1 institution in 1 country.
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Abstract
Aldehyde dehydrogenase 1A1 (ALDH1A1) is one of cancer stem cell (CSC) markers, and high ALDH1 expression has been related to drug resistance and facilitated tumor growth. In this study, we investigated the potential involvement of nuclear factor erythroid 2-like 2 (NFE2L2/NRF2) in CSC-like properties of ALDH-high ovarian CSCs. Our experimental system, ALDH1A1-high (ALDH-H) subpopulation, was isolated and stabilized using doxorubicin-resistant ovarian cancer A2780 cells. ALDH-H exerted CSC-like properties such as drug resistance, colony/sphere formation, and enhanced tumor growth along with high levels of CSCs markers compared to ALDH1A1-low (ALDH-L). Levels of NRF2 and subsequent target genes substantially increased in ALDH-H cells, and the increase in ALDH1A1 and p62 was associated with NRF2 upregulation. ALDH1A1-silencing blocked increases in NRF2, drug efflux transporters, and p62, along with CSC markers in ALDH-H cells. The inhibition of p62, which was elevated in ALDH-H, suppressed NRF2 activation. High NRF2 level was confirmed in the ALDH1-high subpopulation from colon cancer HCT116 cells. The functional implication of NRF2 activation in ovarian CSCs was verified by two experimental approaches. First, CSC-like properties such as high CSC markers, chemoresistance, colony/sphere formation, and tumor growth were significantly inhibited by NRF2-silencing in ALDH-H cells. Second, all-trans retinoic acid (ATRA) suppressed ALDH1 expression, inhibiting NRF2 activation, which led to the attenuation of CSC-like properties in ALDH-H cells but not in ALDH-L cells. These results provide insight into the molecular basis of the ALDH1A1-mediated development of CSC-like properties such as stress/treatment resistance, and further suggest the therapeutic potential of ATRA in ALDH-high ovarian CSCs.
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