ArticleThe Journal of clinical investigation2023
Cancer-associated fibroblast-secreted glucosamine alters the androgen biosynthesis program in prostate cancer via HSD3B1 upregulation.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- HSD3B1 genotype and outcomes in metastatic hormone-sensitive prostate cancer with androgen deprivation therapy and enzalutamide: ARCHES.Cell reports. Medicine · 2024Trial
- Ineffectiveness of immune checkpoint inhibitors in prostate cancer: is it just a question of '-mabs'?The Journal of pathology · 2026Review
- DUSP5 suppresses esophageal squamous cell carcinoma by counteracting macrophage-derived AREG-ERK1/2 signaling and disrupting an oncogenic ERK1/2-ELK1-DUSP5 feedback circuitry.Cell death & disease · 2026Article
- Intratumoral Androgens and Genetic Variants Driving Therapy Resistance in Prostate Cancer.Research (Washington, D.C.) · 2026Review
- The Role of Distinct Cancer-Associated Fibroblast Subtypes in Prostate Cancer Immunotherapy.International journal of biological sciences · 2026Review
- The dual roles of exosomes in prostate cancer: mechanisms in tumorigenesis and avenues for clinical translation.Frontiers in immunology · 2026Review
- Insights into the relevance of targeting fibroblasts to control cancer.Cell reports. Medicine · 2025Review
- PA2G4 in CAFs promotes biochemical recurrence of prostate cancer via H3K18la.Cell & bioscience · 2025Article
- Cancer-associated fibroblasts regulate mitochondrial metabolism and inhibit chemosensitivity via ANGPTL4-IQGAP1 axis in prostate cancer.Journal of advanced research · 2025Article
- Mechanistic Insights and Clinical Implications of ELK1 in Solid Tumors: A Narrative Review.Cells · 2025Review
- Article
- The role of cancer-associated fibroblasts in the tumour microenvironment of urinary system.Clinical and translational medicine · 2025Review
- Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.Journal of hematology & oncology · 2025Review
- Role of exosomes in castration-resistant prostate cancer.Frontiers in oncology · 2025Review
- CAF-mediated regulation of prostate cancer stem cell stemness via the Wnt/β-catenin and SDF-1/CXCR4 pathways in castration-resistant prostate cancer.Frontiers in cell and developmental biology · 2025Article
- PDIA2 is associated with the prognosis of prostate cancer, and downregulation of PDIA2 delays the progression of prostate cancer cells.Scientific reports · 2024Article
- Survival of men with metastatic hormone-sensitive prostate cancer and adrenal-permissive HSD3B1 inheritance.The Journal of clinical investigation · 2024Article
- The multifaceted role of the stroma in the healthy prostate and prostate cancer.Journal of translational medicine · 2024Review
- Prostate Cancer and the Mevalonate Pathway.International journal of molecular sciences · 2024Review
- Chronic hypoxia stabilizes 3βHSD1 via autophagy suppression.Cell reports · 2024Article
Corrections and comments
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- Commented on byUro-Science.2023
Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
After androgen deprivation, prostate cancer frequently becomes castration resistant (CRPC), with intratumoral androgen production from extragonadal precursors that activate the androgen receptor pathway. 3β-Hydroxysteroid dehydrogenase-1 (3βHSD1) is the rate-limiting enzyme for extragonadal androgen synthesis, which together lead to CRPC. Here, we show that cancer-associated fibroblasts (CAFs) increased epithelial 3βHSD1 expression, induced androgen synthesis, activated the androgen receptor, and induced CRPC. Unbiased metabolomics revealed that CAF-secreted glucosamine specifically induced 3βHSD1. CAFs induced higher GlcNAcylation in cancer cells and elevated expression of the transcription factor Elk1, which induced higher 3βHSD1 expression and activity. Elk1 genetic ablation in cancer epithelial cells suppressed CAF-induced androgen biosynthesis in vivo. In patient samples, multiplex fluorescent imaging showed that tumor cells expressed more 3βHSD1 and Elk1 in CAF-enriched areas compared with CAF-deficient areas. Our findings suggest that CAF-secreted glucosamine increases GlcNAcylation in prostate cancer cells, promoting Elk1-induced HSD3B1 transcription, which upregulates de novo intratumoral androgen synthesis to overcome castration.
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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.