ArticleBMC cancer2015
Incomplete Dll4/Notch signaling inhibition promotes functional angiogenesis supporting the growth of skin papillomas.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- Targeting stiffness-dependent YAP/TAZ restores angiogenesis dynamics impaired by ALK1 knockout in silico.PLoS computational biology · 2026Article
- Tensile Stress-Activated and Exosome-Transferred YAP/TAZ-Notch Circuit Specifies Type H Endothelial Cell for Segmental Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- 2Molecular imaging and biology · 2024Article
- Review
- High expression of Dll4 and CD44V6 is associated with clinicopathological characteristics and poor prognosis in osteosarcoma patients.Translational cancer research · 2021Article
- Genetically modified endothelial progenitor cells with hNotch1.ICN overexpression display facilitated angiogenesis.Annals of translational medicine · 2020Article
- The Role of DLLs in Cancer: A Novel Therapeutic Target.OncoTargets and therapy · 2020Review
- Metastasis is impaired by endothelial-specific Dll4 loss-of-function through inhibition of epithelial-to-mesenchymal transition and reduction of cancer stem cells and circulating tumor cells.Clinical & experimental metastasis · 2019Article
- Tumor suppressive effects of the pleiotropically acting miR-195 in colorectal cancer cells.EXCLI journal · 2019Article
- Revision of the concept of anti-angiogenesis and its applications in tumor treatment.Chronic diseases and translational medicine · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundIn invasive malignancies, Dll4/Notch signaling inhibition enhances non-functional vessel proliferation and limits tumor growth by reducing its blood perfusion.
methodsTo assess the effects of targeted Dll4 allelic deletion in the incipient stages of tumor pathogenesis, we chemically induced skin papillomas in wild-type and Dll4 (+/-) littermates, and compared tumor growth, their histological features, vascularization and the expression of angiogenesis-related molecules.
resultsWe observed that Dll4 down-regulation promotes productive angiogenesis, although with less mature vessels, in chemically-induced pre-cancerous skin papillomas stimulating their growth. The increase in endothelial activation was associated with an increase in the VEGFR2 to VEGFR1 ratio, which neutralized the tumor-suppressive effect of VEGFR-targeting sorafenib. Thus, in early papillomas, lower levels of Dll4 increase vascularization through raised VEGFR2 levels, enhancing sensitivity to endogenous levels of VEGF, promoting functional angiogenesis and tumor growth.
conclusionTumor promoting effect of low-dosage inhibition needs to be considered when implementing Dll4 targeting therapies.
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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.