ArticleGynecologic oncology2012
Expression of the Wnt antagonist Dickkopf-3 is associated with prognostic clinicopathologic characteristics and impairs proliferation and invasion in endometrial cancer.
Article in Gynecologic oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Expression Patterns of the Wnt Pathway Inhibitors Dickkopf3 and Secreted Frizzled-Related Proteins 1 and 4 in Endometrial Endometrioid Adenocarcinoma: An NRG Oncology/Gynecologic Oncology Group Study.International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · 2016Trial
- Mitochondrial Abundant Heat Soluble (MAHS) Protein Expression Modulates Metabolic Dynamics in Human Adipose-Derived Stem Cells.International journal of molecular sciences · 2026Article
- RETRACTED: Molecular Investigation of DKK3 in Cerebral Ischemic/Reperfusion Injury.Biomedicines · 2023Article
- Review
- Canine osteosarcoma in comparative oncology: Molecular mechanisms through to treatment discovery.Frontiers in veterinary science · 2022Review
- Addressing activation of WNT beta-catenin pathway in diverse landscape of endometrial carcinogenesis.American journal of translational research · 2021Review
- Cantharidin inhibits osteosarcoma proliferation and metastasis by directly targeting miR-214-3p/DKK3 axis to inactivate β-catenin nuclear translocation and LEF1 translation.International journal of biological sciences · 2021Article
- Article
- Transcriptome analysis of genes related to gonad differentiation and development in Muscovy ducks.BMC genomics · 2020Article
- LncRNA SNHG16 promotes epithelial- mesenchymal transition via down-regulation of DKK3 in gastric cancer.Cancer biomarkers : section A of Disease markers · 2019Article
- Dickkopf-3 Causes Neuroprotection by Inducing Vascular Endothelial Growth Factor.Frontiers in cellular neuroscience · 2018Article
- Review
- Serum biomarker analysis in patients with recurrent spontaneous abortion.Molecular medicine reports · 2017Article
- Cell and matrix response of temporomandibular cartilage to mechanical loading.Osteoarthritis and cartilage · 2016Article
- Dkk3 prevents familial dilated cardiomyopathy development through Wnt pathway.Laboratory investigation; a journal of technical methods and pathology · 2016Article
- Epigenetic silencing of the WNT antagonist Dickkopf 3 disrupts normal Wnt/β-catenin signalling and apoptosis regulation in breast cancer cells.Journal of cellular and molecular medicine · 2013Article
- Article
- p53, SKP2, and DKK3 as MYCN Target Genes and Their Potential Therapeutic Significance.Frontiers in oncology · 2012Article
- 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
8 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveEmerging evidence implicates the Wnt antagonist Dickkopf-3 (Dkk3) as a tumor suppressor and potential biomarker in solid tumors. We investigated whether Dkk3 plays an important role in the carcinogenesis of endometrial cancer (EC).
methodsWe analyzed Dkk3 mRNA expression via real-time RT-PCR in twenty-seven human primary EC tissues, and six matched normal endometrial controls. Dkk3 levels were correlated with various clinicopathologic characteristics. Additionally, enforced Dkk3 expression was examined in proliferation and tumorigenesis in vitro and in vivo, using MTT, soft agar assay, invasion assay, a xenograft mouse model, and a β-catenin-responsive SuperTopFlash luciferase assay.
resultsCompared with matched normal endometrial cases, Dkk3 was down-regulated in EC (p<0.0001). Among cancer cases, Dkk3 expression was significantly reduced in patients with higher stage (p=0.002), positive pelvic lymph nodes (p=0.0004), non-endometrioid histology (p=0.02), and cytology-positive ECs (p=0.02). Enforced expression of Dkk3 in EC cell lines showed reduced proliferation (p<0.0001), anchorage-independent growth (p=0.005), invasion (p=0.02), and reduced TCF activity (p=0.04), confirming Dkk3 as a negative regulator of the β-catenin/Wnt signaling pathway. Tumor growth in Dkk3-injected mice was not statistically different, though did plateau towards the end, and was associated with increased lymphoid infiltration and tumor necrosis.
conclusionDkk3 gene expression is frequently downregulated in endometrial cancer, and is associated with poor prognostic clinicopathologic markers. The results also identify a role for Dkk3 as a tumor suppressor in EC, affecting both proliferation and invasiveness. These findings may prove to be important in the design of novel biomarkers and treatment modalities for advanced EC.
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