ArticleCancer discovery2015
NOTCH decoys that selectively block DLL/NOTCH or JAG/NOTCH disrupt angiogenesis by unique mechanisms to inhibit tumor growth.
Article in Cancer discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 147 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- Review
- Notch receptors in breast cancer: context-dependent roles and therapeutic targeting.Cell communication and signaling : CCS · 2026Review
- Tumor cell Jagged-1 promotes regional lymphatic metastasis and predicts recurrence in node-positive breast cancer.Breast cancer research : BCR · 2026Article
- Notch signaling in the tumor microenvironment: recent advances and targeted therapeutics.Molecular cancer · 2026Review
- FoxO1, together with Notch1, promotes microglial activation to induce pathological changes in the retinal vasculature under hypoxia.Cellular and molecular life sciences : CMLS · 2025Article
- Tumor microenvironment in breast cancer: cellular crosstalk, pathways, and therapeutic insights.Molecular biology reports · 2025Review
- Identifying a prognostic signature for clear cell renal cell carcinoma: the convergence of single-cell and bulk sequencing with machine learning.Frontiers in cell and developmental biology · 2025Article
- Inhibition of Notch4 Using Novel Neutralizing Antibodies Reduces Tumor Growth in Murine Cancer Models by Targeting the Tumor Endothelium.Cancer research communications · 2024Article
- Notch activation defines immune-suppressive subsets of ccRCCs with unfavorable benefits from immunotherapy over VEGFR/mTOR inhibitors.iScience · 2024Article
- Microvascular rarefaction caused by the NOTCH signaling pathway is a key cause of TKI-apatinib-induced hypertension and cardiac damage.Frontiers in pharmacology · 2024Review
- Anoikis-related CTNND1 is associated with immuno-suppressive tumor microenvironment and predicts unfavorable immunotherapeutic outcome in non-small cell lung cancer.Journal of Cancer · 2024Article
- The Potential of JAG Ligands as Therapeutic Targets and Predictive Biomarkers in Multiple Myeloma.International journal of molecular sciences · 2023Article
- Antibody blockade of Jagged1 attenuates choroidal neovascularization.Nature communications · 2023Article
- Notch1 and Notch4 core binding domain peptibodies exhibit distinct ligand-binding and anti-angiogenic properties.Angiogenesis · 2023Article
- Notch Signaling in the Vasculature: Angiogenesis and Angiocrine Functions.Cold Spring Harbor perspectives in medicine · 2023Review
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
- Significance of NotchScore and JAG1 in predicting prognosis and immune response of low-grade glioma.Frontiers in immunology · 2023Article
- Metastasis and cancer associated fibroblasts: taking it up a NOTCH.Frontiers in cell and developmental biology · 2023Review
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
Abstract
unlabelledA proangiogenic role for Jagged (JAG)-dependent activation of NOTCH signaling in the endothelium has yet to be described. Using proteins that encoded different NOTCH1 EGF-like repeats, we identified unique regions of Delta-like ligand (DLL)-class and JAG-class ligand-receptor interactions, and developed NOTCH decoys that function as ligand-specific NOTCH inhibitors. N110-24 decoy blocked JAG1/JAG2-mediated NOTCH1 signaling, angiogenic sprouting in vitro, and retinal angiogenesis, demonstrating that JAG-dependent NOTCH signal activation promotes angiogenesis. In tumors, N110-24 decoy reduced angiogenic sprouting, vessel perfusion, pericyte coverage, and tumor growth. JAG-NOTCH signaling uniquely inhibited expression of antiangiogenic soluble (s) VEGFR1/sFLT1. N11-13 decoy interfered with DLL1-DLL4-mediated NOTCH1 signaling and caused endothelial hypersprouting in vitro, in retinal angiogenesis, and in tumors. Thus, blockade of JAG- or DLL-mediated NOTCH signaling inhibits angiogenesis by distinct mechanisms. JAG-NOTCH signaling positively regulates angiogenesis by suppressing sVEGFR1-sFLT1 and promoting mural-endothelial cell interactions. Blockade of JAG-class ligands represents a novel, viable therapeutic approach to block tumor angiogenesis and growth. SIGNIFICANCE: This is the first report identifying unique regions of the NOTCH1 extracellular domain that interact with JAG-class and DLL-class ligands. Using this knowledge, we developed therapeutic agents that block JAG-dependent NOTCH signaling and demonstrate for the first time that JAG blockade inhibits experimental tumor growth by targeting tumor angiogenesis.
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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.