ArticleJournal of experimental & clinical cancer research : CR2024
Single-cell deconvolution algorithms analysis unveils autocrine IL11-mediated resistance to docetaxel in prostate cancer via activation of the JAK1/STAT4 pathway.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Mapping research trends in macrophage polarization and immunotherapeutic potential in prostate cancer: a bibliometric and visual analysis.Frontiers in oncology · 2026Pooled it
- Anticancer Effects of Fluphenazine Alone and in Combination with Cisplatin in Gastric Cancer Cells and a Mouse Xenograft Model.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Butyrylated PGAM5-Triggered and GSH-Responsive Cysteine Polymer Nanoparticles for CBL0137 Delivery to Enhance Necroptosis in Prostate Cancer.Advanced healthcare materials · 2026Article
- The microbiome across the prostate disease continuum: from health and BPH to prostatitis/CPPS and cancer.Oncogene · 2026Review
- Interleukin-11: A pivotal player and potential therapeutic target in prostate cancer.Current urology · 2026Review
- Generation and characterization of the Il11-Cre knock-in mouse.Transgenic research · 2026Article
- Cancer Cell-Intrinsic Cholesterol Induces Lipid-Associated Macrophage Differentiation via SP1 Palmitoylation to Promote Prostate Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Induction of ferroptosis in prostate cancer by CCDC7Cell death and differentiation · 2026Article
- Tumor microenvironment-driven drug resistance in urologic cancers: mechanisms and therapeutic targets.Genes & genomics · 2026Review
- Identification of interleukin-11 as a comorbid risk factor for prostate cancer and Alzheimer's disease using integrated bioinformatics and machine learning.Frontiers in immunology · 2026Article
- Gut Parabacteroides distasonis-derived Indole-3-Acetic Acid Promotes Phospholipid Remodeling and Enhances Ferroptosis Sensitivity via the AhR-FASN Axis in Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Interleukin-11 promotes lung adenocarcinoma tumourigenesis and immune evasion.Clinical and translational medicine · 2025Article
- The signature based on interleukin family and receptors identified IL19 and IL20RA in promoting nephroblastoma progression through STAT3 pathway.Scientific reports · 2025Article
- Mesenchymal stromal cell exosomes for drug delivery of prostate cancer treatments: a review.Stem cell research & therapy · 2025Review
- Mendelian randomization combined with single-cell sequencing analysis revealed prognostic genes related to myeloid cell differentiation in prostate cancer and experimental verification.Frontiers in immunology · 2025Article
- Metabolic Reprogramming in Urological Tumors: New Perspectives from Tumor Metabolic Phenotypes to Therapeutic Targets.International journal of biological sciences · 2025Review
- Aurora kinase-a expression heterogeneity and potential benefit of combination therapy in prostate adenocarcinoma.Frontiers in cell and developmental biology · 2025Article
- Unleashing the power of peptides in prostate cancer immunotherapy: mechanism, facts and perspectives.Frontiers in pharmacology · 2025Review
- Correction: Single-cell deconvolution algorithms analysis unveils autocrine IL11-mediated resistance to docetaxel in prostate cancer via activation of the JAK1/STAT4 pathway.Journal of experimental & clinical cancer research : CR · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDocetaxel resistance represents a significant obstacle in the treatment of prostate cancer. The intricate interplay between cytokine signalling pathways and transcriptional control mechanisms in cancer cells contributes to chemotherapeutic resistance, yet the underlying molecular determinants remain only partially understood. This study elucidated a novel resistance mechanism mediated by the autocrine interaction of interleukin-11 (IL-11) and its receptor interleukin-11 receptor subunit alpha(IL-11RA), culminating in activation of the JAK1/STAT4 signalling axis and subsequent transcriptional upregulation of the oncogene c-MYC.
methodsSingle-cell secretion profiling of prostate cancer organoid was analyzed to determine cytokine production profiles associated with docetaxel resistance.Analysis of the expression pattern of downstream receptor IL-11RA and enrichment of signal pathway to clarify the potential autocrine mechanism of IL-11.Next, chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) was performed to detect the nuclear localization and DNA-binding patterns of phosphorylated STAT4 (pSTAT4). Coimmunoprecipitation and reporter assays were utilized to assess interaction between pSTAT4 and the cotranscription factor CREB-binding protein (CBP) as well as their role in c-MYC transcriptional activity.
resultsAutocrine secretion of IL-11 was markedly increased in docetaxel-resistant prostate cancer cells. IL-11 stimulation resulted in robust activation of JAK1/STAT4 signalling. Upon activation, pSTAT4 translocated to the nucleus and associated with CBP at the c-MYC promoter region, amplifying its transcriptional activity. Inhibition of the IL-11/IL-11RA interaction or disruption of the JAK1/STAT4 pathway significantly reduced pSTAT4 nuclear entry and its binding to CBP, leading to downregulation of c-MYC expression and restoration of docetaxel sensitivity.
conclusionOur findings identify an autocrine loop of IL-11/IL-11RA that confers docetaxel resistance through the JAK1/STAT4 pathway. The pSTAT4-CBP interaction serves as a critical enhancer of c-MYC transcriptional activity in prostate cancer cells. Targeting this signalling axis presents a potential therapeutic strategy to overcome docetaxel resistance in advanced prostate cancer.
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