ArticleOncogene2012
Dickkopf 4 (DKK4) acts on Wnt/β-catenin pathway by influencing β-catenin in hepatocellular carcinoma.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- DKK1 Overexpression in Lung Adenocarcinoma: Prognostic Implications, Immune Microenvironment Correlates, and Regulatory Network Characterization.Biological procedures online · 2025Article
- Therapeutic effects of topical Mycophenolate mofetil on hydroquinone-induced depigmentation in Guinea pigs and mice.Annals of medicine · 2025Article
- CYP2E1 overexpression in hepatocellular carcinoma modulates tumor invasion and migration via Wnt/β-catenin signaling pathway.Journal of molecular histology · 2025Article
- Single-Cell RNA Sequencing Reveals LEF1-Driven Wnt Pathway Activation as a Shared Oncogenic Program in Hepatoblastoma and Medulloblastoma.Current oncology (Toronto, Ont.) · 2025Article
- Colorectal cancer cells secreting DKK4 transform fibroblasts to promote tumour metastasis.Oncogene · 2024Article
- The correlation between cancer stem cells and epithelial-mesenchymal transition: molecular mechanisms and significance in cancer theragnosis.Frontiers in immunology · 2024Review
- Dickkopf 4 Alone and in Combination with Leucyl-tRNA Synthetase as a Good Prognostic Biomarker for Human Colorectal Cancer.BioMed research international · 2023Article
- Wnt antagonist as therapeutic targets in ovarian cancer.The international journal of biochemistry & cell biology · 2022Review
- Dickkopf Proteins and Their Role in Cancer: A Family of Wnt Antagonists with a Dual Role.Pharmaceuticals (Basel, Switzerland) · 2021Review
- A literature review on function and regulation mechanism of DKK4.Journal of cellular and molecular medicine · 2021Review
- Methylation Assessment of TwoIranian journal of public health · 2020Article
- Anti proliferative and apoptotic effects on pancreatic cancer cell lines indicate new roles for ANGPTL8 (Betatrophin).Genetics and molecular biology · 2020Article
- Sensitization of hepatocellular carcinoma cells towards doxorubicin and sorafenib is facilitated by glucosedependent alterations in reactive oxygen species, P-glycoprotein and DKK4.Journal of biosciences · 2020Article
- Angiopoietin-like protein 8 (betatrophin) may inhibit hepatocellular carcinoma through suppressing of the Wnt signaling pathway.Iranian journal of basic medical sciences · 2019Article
- Aberrant accumulation of Dickkopf 4 promotes tumor progression via forming the immune suppressive microenvironment in gastrointestinal stromal tumor.Cancer medicine · 2019Article
- LRP16 prevents hepatocellular carcinoma progression through regulation of Wnt/β-catenin signaling.Journal of molecular medicine (Berlin, Germany) · 2018Article
- Role of DKK4 in Tumorigenesis and Tumor Progression.International journal of biological sciences · 2018Review
- Serine peptidase inhibitor Kazal type 1 (SPINK1) as novel downstream effector of the cadherin-17/β-catenin axis in hepatocellular carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2017Article
- Wnt/β-catenin Signaling Contributes to Tumor Malignancy and Is Targetable in Gastrointestinal Stromal Tumor.Molecular cancer therapeutics · 2017Article
- Dickkopf-4 is frequently overexpressed in epithelial ovarian carcinoma and promotes tumor invasion.BMC cancer · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deregulation of Wnt/β-catenin pathway is a hallmark of major gastrointestinal cancers including hepatocellular carcinoma (HCC). The oncogenic role of β-catenin is well defined but reasons for its accumulation in HCC remain unclear. Dickkopf 4 (DKK4) acts as a negative regulator of Wnt/β-catenin pathway but its functional role in liver carcinogenesis has not been studied. We investigated the role of DKK4 in β-catenin regulation in HCC. Reduced expression of DKK4 was found in 47% (38/81) of HCC, as measured by quantitative real time PCR. Ectopic expression of DKK4 in two HCC cell lines, PLC/PRF/5 (PLC) and MHCC97L (97L), attenuated β-catenin responsive luciferase activity, and decreased both β-catenin and cyclin D1 protein levels. To study the effect of DKK4 on cell growth and tumourigenicity, two stable HCC cell lines were established from PLC and 97L cells. Functional assays demonstrated that overexpression of DKK4 hampered cell proliferation, reduced colony formation and retarded cell migration. When DKK4-expressing 97L stable cells were used to induce tumour xenografts in nude mice (n=8), reduction in tumour sizes was observed (P=0.027). Furthermore, immunohistochemical studies showed that decreased expression of DKK4 was associated with β-catenin accumulation in HCC tissues. Additionally, inhibition of the proteasome using specific inhibitor in DKK4-expressing 97L stable cells masked the effect of β-catenin. Our findings suggest a potential tumour suppressive role of DKK4 as well as that of an important regulator of HCC.
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