ArticleThe Prostate2013
Dickkopf-related protein 3 promotes pathogenic stromal remodeling in benign prostatic hyperplasia and prostate cancer.
Article in The Prostate, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Antibody screening identifies HERV-K-related immune responses as candidate biomarkers in Parkinson's disease.Frontiers in cellular and infection microbiology · 2026Article
- Intrinsic and extrinsic factors causing hyperplasia of the prostate.International journal of urology : official journal of the Japanese Urological Association · 2024Review
- The Multifaceted Role of Human Dickkopf-3 (DKK-3) in Development, Immune Modulation and Cancer.Cells · 2023Review
- Mechanism of Androgen-Independent Stromal Proliferation in Benign Prostatic Hyperplasia.International journal of molecular sciences · 2023Review
- Article
- Review
- Dickkopf-3 (DKK3) Signaling in IL-1α-Challenged Chondrocytes: Involvement of the NF-κB Pathway.Cartilage · 2021Article
- Vitamin D sufficiency enhances differentiation of patient-derived prostate epithelial organoids.iScience · 2021Article
- The Impact of CRISPR-Cas9 on Age-related Disorders: From Pathology to Therapy.Aging and disease · 2020Review
- The Suppressing Effects of Dkk3 Expression on Aggressiveness and Tumorigenesis of Colorectal Cancer.Frontiers in oncology · 2020Article
- Suppression of stromal-derived Dickkopf-3 (DKK3) inhibits tumor progression and prolongs survival in pancreatic ductal adenocarcinoma.Science translational medicine · 2018Article
- Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1.Oncogene · 2018Article
- CRISPR-Mediated Reactivation of DKK3 Expression Attenuates TGF-β Signaling in Prostate Cancer.Cancers · 2018Article
- Secretory factors from OP9 stromal cells delay differentiation and increase the expansion potential of adult erythroid cells in vitro.Scientific reports · 2018Article
- DKK3 Overexpression Increases the Malignant Properties of Head and Neck Squamous Cell Carcinoma Cells.Oncology research · 2018Article
- Screening of potential therapy targets for prostate cancer using integrated analysis of two gene expression profiles.Oncology letters · 2017Article
- Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia.International journal of molecular sciences · 2016Review
- Article
- DKK3 blocked translocation of β-catenin/EMT induced by hypoxia and improved gemcitabine therapeutic effect in pancreatic cancer Bxpc-3 cell.Journal of cellular and molecular medicine · 2015Article
- Single nucleotide polymorphisms in DKK3 gene are associated with prostate cancer risk and progression.International braz j urol : official journal of the Brazilian Society of UrologyArticle
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCompartment-specific epithelial and stromal expression of the secreted glycoprotein Dickkopf-related protein (Dkk)-3 is altered in age-related proliferative disorders of the human prostate. This study aimed to determine the effect of Dkk-3 on prostate stromal remodeling that is stromal proliferation, fibroblast-to-myofibroblast differentiation and expression of angiogenic factors in vitro.
methodsLentiviral-delivered overexpression and shRNA-mediated knockdown of DKK3 were applied to primary human prostatic stromal cells (PrSCs). Cellular proliferation was analyzed by BrdU incorporation ELISA. Expression of Dkk-3, apoptosis-related genes, cyclin-dependent kinase inhibitors and angiogenic factors were analyzed by qPCR, Western blot analysis or ELISA. Fibroblast-to-myofibroblast differentiation was monitored by smooth muscle cell actin and insulin-like growth factor binding protein 3 mRNA and protein levels. The relevance of Wnt/β-catenin and PI3K/AKT signaling pathways was assessed by cytoplasmic/nuclear β-catenin levels and phosphorylation of AKT.
resultsKnockdown of DKK3 significantly attenuated PrSC proliferation as well as fibroblast-to-myofibroblast differentiation and increased the expression of the vessel stabilizing factor angiopoietin-1. DKK3 knockdown did not affect subcellular localization or levels of β-catenin but attenuated AKT phosphorylation in PrSCs. Consistently the PI3K/AKT inhibitor LY294002 mimicked the effects of DKK3 knockdown.
conclusionsDkk-3 promotes fibroblast proliferation and myofibroblast differentiation and regulates expression of angiopoietin-1 in prostatic stroma potentially via enhancing PI3K/AKT signaling. Thus, elevated Dkk-3 in the stroma of the diseased prostate presumably regulates stromal remodeling by enhancing proliferation and differentiation of stromal cells and contributing to the angiogenic switch observed in BPH and PCa. Therefore, Dkk-3 represents a potential therapeutic target for stromal remodeling in BPH and PCa.
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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.