ArticleCell communication and signaling : CCS2022
The ERα-NRF2 signalling axis promotes bicalutamide resistance in prostate cancer.
Article in Cell communication and signaling : CCS, 2022. 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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18 citing papers in PubMed, 16 citations in OpenAlex.
- Unfolded Protein Response Pathways in Cancer: Mechanisms, Tumor Biology and Therapeutic Opportunities.Molecular diagnosis & therapy · 2026Review
- DNMT1-DUOXA1 axis discovers a novel methylation-ferroptosis circuit in bicalutamide-resistant prostate cancer.Redox biology · 2026Article
- The role of NRF2 in human cancers: Pre-clinical insights paving the way for clinical trials.Journal of pharmaceutical analysis · 2026Review
- The role of estrogen and its receptors in the regulation of ferroptosis and autophagy.Molecular biology reports · 2026Review
- Inflammaging: Immune-Metabolic Crosstalk Between the Prostate-Testis and Musculoskeletal System.International journal of molecular sciences · 2026Review
- ROS-Fueled Allies: STAT3, PKM2, and HIF-1α Influencing Energy Metabolism in Hormone-Independent Cancers.International journal of molecular sciences · 2026Article
- Seasonal summer stress affects systemic redox homeostasis: a longitudinal marker analysis in healthy adults.Frontiers in public health · 2026Article
- The Role of Estrogen Signaling Pathway and Targeted Therapy Exploration in Urological Tumors.International journal of biological sciences · 2026Review
- NRF2 deficiency leads to inadequate beta cell adaptation during pregnancy and gestational diabetes.Redox biology · 2025Article
- Parkinson's disease and glucose metabolism impairment.Translational neurodegeneration · 2025Review
- PGK1 Regulates Oxidative Stress in Gestational Diabetes Mellitus through the Estradiol-Keap1-Nrf2 Pathway.International journal of biological sciences · 2025Article
- Antioxidant 1,2,3,4,6-Penta-Molecules (Basel, Switzerland) · 2024Article
- Effectiveness of Tri-Kaysorn-Mas Extract in Ameliorating Cognitive-like Behavior Deficits in Ovariectomized Mice via Activation of Multiple Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Androgen receptor and estrogen receptor variants in prostate and breast cancers.The Journal of steroid biochemistry and molecular biology · 2024Review
- Dynamic interplay of nuclear receptors in tumor cell plasticity and drug resistance: Shifting gears in malignant transformations and applications in cancer therapeutics.Cancer metastasis reviews · 2024Review
- Nrf2 in human cancers: biological significance and therapeutic potential.American journal of cancer research · 2024Review
- MiR-15b-3p weakens bicalutamide sensitivity in prostate cancer via targeting KLF2 to suppress ferroptosis.Journal of Cancer · 2024Article
- Molecular Insight into Prostate Cancer: Preventive Role of Selective Bioactive Molecules.Life (Basel, Switzerland) · 2023Review
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBicalutamide is a nonsteroidal antiandrogen widely used as a first-line clinical treatment for advanced prostate cancer (PCa). Although patients initially show effective responses to bicalutamide treatment, resistance to bicalutamide frequently occurs and leads to the development of castration-resistant PCa (CRPC). This research investigated the roles of the oestrogen receptor α (ERα)-nuclear factor E2-related factor 2 (NRF2) signalling pathway in bicalutamide resistance in PCa cells.
methodsWe performed bioinformatic analysis and immunohistochemical staining on normal and cancerous prostate tissue to evaluate ERα and NRF2 expression and their correlation. Gene expression and localization in PCa cell lines were further investigated using real-time reverse transcription PCR/Western blotting and immunofluorescence staining. We treated PCa cells with the ER inhibitor tamoxifen and performed luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays to understand ERα-dependent NRF2 expression. Overexpression and knockdown of ERα and NRF2 were used to explore the potential role of the ERα-NRF2 signalling axis in bicalutamide resistance in PCa cells.
resultsWe found that the expression of ERα and NRF2 was positively correlated and was higher in human CRPC tissues than in primary PCa tissues. Treatment with oestrogen or bicalutamide increased the expression of ERα and NRF2 as well as NRF2 target genes in PCa cell lines. These effects were blocked by pretreatment with tamoxifen. ChIP assays demonstrated that ERα directly binds to the oestrogen response element (ERE) in the NRF2 promoter. This binding led to increased transcriptional activity of NRF2 in a luciferase reporter assay. Activation of the ERα-NRF2 signalling axis increased the expression of bicalutamide resistance-related genes. Inhibition of this signalling axis by knockdown of ERα or NRF2 downregulated the expression of bicalutamide resistance-related genes and inhibited the proliferation and migration of PCa cells.
conclusionsWe demonstrated the transcriptional interaction between ERα and NRF2 in CRPC tissues and cell lines by showing the direct binding of ERα to the ERE in the NRF2 promoter under oestrogen treatment. Activation of the ERα-NRF2 signalling axis contributes to bicalutamide resistance in PCa cells, suggesting that the ERα-NRF2 signalling axis is a potential therapeutic target for CRPC. Video Abstract.
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