ArticlePloS one2016
Loss of Dickkopf 3 Promotes the Tumorigenesis of Basal Breast Cancer.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Ad-SGE-DKK3 Gene Therapy Overcomes Resistance to Immune Checkpoint Blockade in Pleural Mesothelioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Evaluation of the Clinical Value of the Serological Markers CD276 and DKK3 in Gastric Cancer: A Case-Control Study.Diagnostics (Basel, Switzerland) · 2026Article
- Unraveling the Multifaceted Role of the miR-17-92 Cluster in Colorectal Cancer: From Mechanisms to Biomarker Potential.Current issues in molecular biology · 2024Review
- The prognostic value of Dickkopf-3 (Dkk3), TGFB1 and ECM-1 in prostate cancer.Frontiers in molecular biosciences · 2024Article
- Predictive value of glycoprotein DKK3 for early neurological deterioration after ischemic stroke.Clinics (Sao Paulo, Brazil) · 2024Article
- Impact of Altered Body Composition on Clinical and Oncological Outcomes in Intrahepatic Cholangiocarcinoma.Journal of clinical medicine · 2023Article
- Dormant tumors circumvent tumor-specific adaptive immunity by establishing a Treg-dominated niche via DKK3.JCI insight · 2023Article
- Article
- Methylation Patterns ofCancers · 2021Article
- Wnt Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2021Article
- Inhibition of the Wnt Signalling Pathway: An Avenue to Control Breast Cancer Aggressiveness.International journal of molecular sciences · 2020Review
- Angioregulatory microRNAs in Colorectal Cancer.Cancers · 2019Review
- Dickkopf Homolog 3Frontiers in oncology · 2019Article
- LncRNA SNHG16 promotes epithelial- mesenchymal transition via down-regulation of DKK3 in gastric cancer.Cancer biomarkers : section A of Disease markers · 2019Article
- TLR-4/Wnt modulation as new therapeutic strategy in the treatment of glioblastomas.Oncotarget · 2018Article
- Machine learning identifies a core gene set predictive of acquired resistance to EGFR tyrosine kinase inhibitor.Journal of cancer research and clinical oncology · 2018Article
- High-frequency deregulated expression of Wnt signaling pathway members in breast carcinomas.OncoTargets and therapy · 2018Article
- Dickkopf-3 Causes Neuroprotection by Inducing Vascular Endothelial Growth Factor.Frontiers in cellular neuroscience · 2018Article
- Methylation of the DKK3 promoter is associated with poor prognosis in patients with cervical adenocarcinoma.International journal of clinical and experimental pathology · 2018Article
- Modulation of Dkk-3 and claudin-5 as new therapeutic strategy in the treatment of meningiomas.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dickkopf 3 (DKK3) has been associated with tumor suppression of various tumor entities including breast cancer. However, the functional impact of DKK3 on the tumorigenesis of distinct molecular breast cancer subtypes has not been considered so far. Therefore, we initiated a study analyzing the subtype-specific DKK3 expression pattern as well as its prognostic and functional impact with respect to breast cancer subtypes. Based on three independent tissue cohorts including one in silico dataset (n = 30, n = 463 and n = 791) we observed a clear down-regulation of DKK3 expression in breast cancer samples compared to healthy breast tissue controls on mRNA and protein level. Interestingly, most abundant reduction of DKK3 expression was detected in the highly aggressive basal breast cancer subtype. Analyzing a large in silico dataset comprising 3,554 cases showed that low DKK3 mRNA expression was significantly associated with reduced recurrence free survival (RFS) of luminal and basal-like breast cancer cases. Functionally, DKK3 re-expression in human breast cancer cell lines led to suppression of cell growth possibly mediated by up-regulation of apoptosis in basal-like but not in luminal-like breast cancer cell lines. Moreover, ectopic DKK3 expression in mesenchymal basal breast cancer cells resulted in partial restoration of epithelial cell morphology which was molecularly supported by higher expression of epithelial markers like E-Cadherin and down-regulation of mesenchymal markers such as Snail 1. Hence, we provide evidence that down-regulation of DKK3 especially promotes tumorigenesis of the aggressive basal breast cancer subtype. Further studies decoding the underlying molecular mechanisms of DKK3-mediated effects may help to identify novel targeted therapies for this clinically highly relevant breast cancer subtype.
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