ArticleOncogenesis2016
Jagged 1 is a major Notch ligand along cholangiocarcinoma development in mice and humans.
Article in Oncogenesis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The trial behind it
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Who cites it
22 citing papers in PubMed, 74 citations in OpenAlex.
- Preclinical mouse models for studying cholangiocarcinoma.Liver research (Beijing, China) · 2026Review
- Molecular Alterations and Pathways in Intrahepatic Cholangiocarcinoma: Available Evidence and New Perspectives.International journal of molecular sciences · 2025Review
- Oncogenic plasmid DNA and liver injury agent dictates liver cancer development in a mouse model.Clinical science (London, England : 1979) · 2024Article
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Angiogenic signaling pathways and anti-angiogenic therapy for cancer.Signal transduction and targeted therapy · 2023Review
- Crenigacestat blocking notch pathway reduces liver fibrosis in the surrounding ecosystem of intrahepatic CCA viaTGF-β inhibition.Journal of experimental & clinical cancer research : CR · 2022Article
- The Hippo pathway effector TAZ induces intrahepatic cholangiocarcinoma in mice and is ubiquitously activated in the human disease.Journal of experimental & clinical cancer research : CR · 2022Article
- Notch signaling in the pathogenesis, progression and identification of potential targets for cholangiocarcinoma (Review).Molecular and clinical oncology · 2022Review
- Focal adhesion kinase (FAK) promotes cholangiocarcinoma development and progression via YAP activation.Journal of hepatology · 2021Article
- Cell of origin in biliary tract cancers and clinical implications.JHEP reports : innovation in hepatology · 2021Review
- Alagille syndrome and risk for hepatocellular carcinoma: Need for increased surveillance in adults with mild liver phenotypes.American journal of medical genetics. Part A · 2021Article
- Article
- Notch signalling pathway in development of cholangiocarcinoma.World journal of gastrointestinal oncology · 2020Review
- Crenigacestat, a selective NOTCH1 inhibitor, reduces intrahepatic cholangiocarcinoma progression by blocking VEGFA/DLL4/MMP13 axis.Cell death and differentiation · 2020Article
- The Hippo Effector Transcriptional Coactivator with PDZ-Binding Motif Cooperates with Oncogenic β-Catenin to Induce Hepatoblastoma Development in Mice and Humans.The American journal of pathology · 2020Article
- Axis inhibition protein 1 (Axin1) Deletion-Induced Hepatocarcinogenesis Requires Intact β-Catenin but Not Notch Cascade in Mice.Hepatology (Baltimore, Md.) · 2019Article
- Review
- The role of tumour microenvironment: a new vision for cholangiocarcinoma.Journal of cellular and molecular medicine · 2019Review
- Article
- Differentiation-inducing therapeutic effect of Notch inhibition in reversing malignant transformation of liver normal stem cells via MET.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 4 countries.
Funding
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a rare yet deadly malignancy with limited treatment options. Activation of the Notch signalling cascade has been implicated in cholangiocarcinogenesis. However, while several studies focused on the Notch receptors required for ICC development, little is known about the upstream inducers responsible for their activation. Here, we show that the Jagged 1 (Jag1) ligand is almost ubiquitously upregulated in human ICC samples when compared with corresponding non-tumorous counterparts. Furthermore, we found that while overexpression of Jag1 alone does not lead to liver tumour development, overexpression of Jag1 synergizes with activated AKT signalling to promote liver carcinogenesis in AKT/Jag1 mice. Histologically, tumours consisted exclusively of ICC, with hepatocellular tumours not occurring in AKT/Jag1 mice. Furthermore, tumours from AKT/Jag1 mice exhibited extensive desmoplastic reaction, an important feature of human ICC. At the molecular level, we found that both AKT/mTOR and Notch cascades are activated in AKT/Jag1 ICC tissues, and that the Notch signalling is necessary for ICC development in AKT/Jag1 mice. In human ICC cell lines, silencing of Jag1 via specific small interfering RNA reduces proliferation and increases apoptosis. Finally, combined inhibition of AKT and Notch pathways is highly detrimental for the in vitro growth of ICC cell lines. In summary, our study demonstrates that Jag1 is an important upstream inducer of the Notch signalling in human and mouse ICC. Targeting Jag1 might represent a novel therapeutic strategy for the treatment of this deadly disease.
Identifiers
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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.