ArticleThe Journal of clinical investigation2015
WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
154 citing papers in PubMed, 273 citations in OpenAlex.
- Comprehensive Analyses of SOX7 Provide Novel Insights on Its Tumor Suppressor Role and Its Target Genes with Therapeutic Implications in Multiple Myeloma.International journal of molecular sciences · 2026Article
- Advances in the Molecular Mechanisms of Cholangiocarcinoma: A Comprehensive Review of Biomarkers, Regulatory Pathways and Tumor Microenvironment Reprogramming.International journal of molecular sciences · 2026Review
- Article
- Signalling pathways in hepatocellular carcinoma (HCC) metastasis and invasion: Molecular mechanisms and therapeutic implications.Biochemistry and biophysics reports · 2026Review
- Cholangiocarcinoma 2026: status quo, unmet needs and priorities.Nature reviews. Gastroenterology & hepatology · 2026Review
- Stratifying cholangiocarcinoma: tumor microenvironment, molecular drivers, and novel immunotherapeutic approaches.Clinical and molecular hepatology · 2026Review
- The macrophage opera: from metabolic prolog to oncogenic crescendo in metabolic dysfunction-associated steatotic liver disease.Frontiers in medicine · 2026Review
- Molecular mechanisms and genetic features of cholangiocarcinoma: implications for targeted therapeutic strategies.Precision clinical medicine · 2025Review
- Primary Cilia in Hepatic Biliary Hyperplasia: Implications for Liver Diseases.Seminars in liver disease · 2025Review
- Genetic, Epigenetic, and Microenvironmental Drivers of Cholangiocarcinoma.The American journal of pathology · 2025Review
- Liver diseases: epidemiology, causes, trends and predictions.Signal transduction and targeted therapy · 2025Review
- Review
- 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
- Wnt/β-Catenin Signaling in Liver Pathobiology.Annual review of pathology · 2025Review
- The Immune Landscape and Its Potential for Immunotherapy in Advanced Biliary Tract Cancer.Current oncology (Toronto, Ont.) · 2024Review
- WNT signaling contributes to the extrahepatic bile duct proliferative response to obstruction in mice.JCI insight · 2024Article
- 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
- Review
94 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Cholangiocarcinoma (CC) is typically diagnosed at an advanced stage and is refractory to surgical intervention and chemotherapy. Despite a global increase in the incidence of CC, little progress has been made toward the development of treatments for this cancer. Here we utilized human tissue; CC cell xenografts; a p53-deficient transgenic mouse model; and a non-transgenic, chemically induced rat model of CC that accurately reflects both the inflammatory and regenerative background associated with human CC pathology. Using these systems, we determined that the WNT pathway is highly activated in CCs and that inflammatory macrophages are required to establish this WNT-high state in vivo. Moreover, depletion of macrophages or inhibition of WNT signaling with one of two small molecule WNT inhibitors in mouse and rat CC models markedly reduced CC proliferation and increased apoptosis, resulting in tumor regression. Together, these results demonstrate that enhanced WNT signaling is a characteristic of CC and suggest that targeting WNT signaling pathways has potential as a therapeutic strategy for CC.
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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.