ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2014
Activated macrophages promote Wnt/β-catenin signaling in cholangiocarcinoma cells.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 104 citations in OpenAlex.
- A randomized placebo-controlled phase I clinical trial to evaluate the immunomodulatory activities of Atractylodes lancea (Thunb) DC. in healthy Thai subjects.BMC complementary medicine and therapies · 2021Trial
- Molecular mechanisms and genetic features of cholangiocarcinoma: implications for targeted therapeutic strategies.Precision clinical medicine · 2025Review
- Wnt/β-Catenin Signaling in Liver Pathobiology.Annual review of pathology · 2025Review
- Epigenetic regulation of individual components of combined hepatocellular-cholangiocarcinoma.PloS one · 2025Article
- Targeting the tumor microenvironment in cholangiocarcinoma to improve immune checkpoint blockade: potential strategies and translational pre-clinical models.Clinical & translational immunology · 2025Review
- Multi-Omics Profiling Unveils the Complexity and Dynamics of Immune Infiltrates in Intrahepatic Cholangiocarcinoma.Biology · 2024Article
- Signaling pathways in liver cancer: pathogenesis and targeted therapy.Molecular biomedicine · 2024Review
- Article
- Research hotspots and trends in immunotherapy for cholangiocarcinoma: a bibliometric analysis (2014-2023).Frontiers in immunology · 2024Article
- Overcoming treatment resistance in cholangiocarcinoma: current strategies, challenges, and prospects.Frontiers in cell and developmental biology · 2024Review
- Glucan fromJournal of Cancer · 2024Article
- Tumor immune microenvironment and the current immunotherapy of cholangiocarcinoma (Review).International journal of oncology · 2023Review
- Immunobiology of cholangiocarcinoma.Journal of hepatology · 2023Review
- Infectious Agents Induce Wnt/β-Catenin Pathway Deregulation in Primary Liver Cancers.Microorganisms · 2023Review
- Review
- Immune microenvironment of cholangiocarcinoma: Biological concepts and treatment strategies.Frontiers in immunology · 2023Review
- PRDX6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma.Medical oncology (Northwood, London, England) · 2022Article
- Targeting ligand-dependent wnt pathway dysregulation in gastrointestinal cancers through porcupine inhibition.Pharmacology & therapeutics · 2022Review
- Tumor specificity of WNT ligands and receptors reveals universal squamous cell carcinoma oncogenes.BMC cancer · 2022Article
- Targeting Wnt/β-Catenin Pathways in Primary Liver Tumours: From Microenvironment Signaling to Therapeutic Agents.Cancers · 2022Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The Wnt/β-catenin signaling pathway is pathologically activated in cholangiocarcinoma (CCA). Here, we determined the expression profile as well as biological role of activated Wnt/β-catenin signaling in CCA. The quantitative reverse transcription polymerase chain reaction demonstrated that Wnt3a, Wnt5a, and Wnt7b mRNA were significantly higher in CCA tissues than adjacent non-tumor tissues and normal liver tissues. Immunohistochemical staining revealed that Wnt3a, Wnt5a, and Wnt7b were positive in 92.1, 76.3, and 100 % of 38 CCA tissues studied. It was noted that Wnt3 had a low expression in tumor cells, whereas a high expression was mainly found in inflammatory cells. Interestingly, a high expression level of Wnt5a was significantly correlated to poor survival of CCA patients (P=0.009). Membrane localization of β-catenin was reduced in the tumors compared to normal bile duct epithelia, and we also found that 73.7 % of CCA cases showed the cytoplasmic localization. Inflammation is known to be a risk factor for CCA development, and we tested whether this might induce Wnt/β-catenin signaling. We found that lipopolysaccharides (LPS) elevated the expression of Wnt3 both mRNA and protein levels in the macrophage cell line. Additionally, the conditioned media taken from LPS-induced activated macrophage culture promoted β-catenin accumulation in CCA cells. Furthermore, transient suppression of β-catenin by siRNA significantly induced growth inhibition of CCA cells, concurrently with decreasing cyclin D1 protein level. In conclusion, the present study reports the abundant expression of Wnt protein family and β-catenin in CCA as well as the effect of inflammatory condition on Wnt/β-catenin activation in CCA cells. Importantly, abrogation of β-catenin expression caused significant CCA cell growth inhibition. Thus, the Wnt/β-catenin signaling pathway may contribute to CCA cell proliferation and hence may serve as a prognostic marker for CCA progression and provide a potential target for CCA therapy.
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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.