ArticleVascular cell2013
Notch4 is required for tumor onset and perfusion.
Article in Vascular cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 15 citations in OpenAlex.
- Notch receptors in breast cancer: context-dependent roles and therapeutic targeting.Cell communication and signaling : CCS · 2026Review
- NOTCH4 as a driver of epithelial-mesenchymal transition, angiogenesis, and stromal remodeling in lung adenocarcinoma: integrated transcriptomic and protein-level validation.Translational lung cancer research · 2026Article
- Notch signaling pathway modulation by food functional ingredients: mechanisms, cancer and immunoregulation.Frontiers in cell and developmental biology · 2025Review
- Inhibition of Notch4 Using Novel Neutralizing Antibodies Reduces Tumor Growth in Murine Cancer Models by Targeting the Tumor Endothelium.Cancer research communications · 2024Article
- Notch1 and Notch4 core binding domain peptibodies exhibit distinct ligand-binding and anti-angiogenic properties.Angiogenesis · 2023Article
- Unique functions for Notch4 in murine embryonic lymphangiogenesis.Angiogenesis · 2022Article
- Targeting Notch4 in Cancer: Molecular Mechanisms and Therapeutic Perspectives.Cancer management and research · 2021Review
- LncRNA PPM1A-AS Regulate Tumor Development Through Multiple Signal Pathways in T-Cell Acute Lymphoblastic Leukemia.Frontiers in oncology · 2021Article
- Association between single nucleotide polymorphisms ofCancer management and research · 2019Article
- Article
- The Notch Pathway in Breast Cancer Progression.TheScientificWorldJournal · 2018Review
- AKT and 14-3-3 regulate Notch4 nuclear localization.Scientific reports · 2015Article
- Novel expression of EGFL7 in placental trophoblast and endothelial cells and its implication in preeclampsia.Mechanisms of development · 2014Article
- Global gene expression changes induced by prolonged cold ischemic stress and preservation method of breast cancer tissue.Molecular oncology · 2014Article
- Delta-like ligand 4 (DLL4) in the plasma and neoplastic tissues from breast cancer patients: correlation with metastasis.Medical oncology (Northwood, London, England) · 2014Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNotch4 is a member of the Notch family of receptors that is primarily expressed in the vascular endothelial cells. Genetic deletion of Notch4 does not result in an overt phenotype in mice, thus the function of Notch4 remains poorly understood.
methodsWe examined the requirement for Notch4 in the development of breast cancer vasculature. Orthotopic transplantation of mouse mammary tumor cells wild type for Notch4 into Notch4 deficient hosts enabled us to delineate the contribution of host Notch4 independent of its function in the tumor cell compartment.
resultsHere, we show that Notch4 expression is required for tumor onset and early tumor perfusion in a mouse model of breast cancer. We found that Notch4 expression is upregulated in mouse and human mammary tumor vasculature. Moreover, host Notch4 deficiency delayed the onset of MMTV-PyMT tumors, wild type for Notch4, after transplantation. Vessel perfusion was decreased in tumors established in Notch4-deficient hosts. Unlike in inhibition of Notch1 or Dll4, vessel density and branching in tumors developed in Notch4-deficient mice were unchanged. However, final tumor size was similar between tumors grown in wild type and Notch4 null hosts.
conclusionOur results suggest a novel role for Notch4 in the establishment of tumor colonies and vessel perfusion of transplanted mammary tumors.
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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.