ArticleJournal of cellular and molecular medicine2013
Loss of CCM3 impairs DLL4-Notch signalling: implication in endothelial angiogenesis and in inherited cerebral cavernous malformations.
Article in Journal of cellular and molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Molecular Pathways and Circulating Biomarkers in Cerebral Cavernous Malformations-A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Prenatal SEB Exposure Triggers Biphasic Notch Signaling Modulation in Offspring Thymus From Neonatal Suppression to Adult Activation.Journal of applied toxicology : JAT · 2026Article
- Article
- Identification of the adhesion GPCR ADGRL4/ELTD1 as a novel potential prognostic biomarker for cerebral cavernous malformation disease.Molecular medicine (Cambridge, Mass.) · 2026Article
- Tumor-like proliferation of CCM3 knockout endothelial cells: insights from semaxinib treatment and transcriptome profiling of co-cultures.Acta neuropathologica communications · 2026Article
- The Notch1 intracellular domain orchestrates mechanotransduction of fluid shear stress.Life science alliance · 2026Article
- FMDV 3A cooperates with PDCD10 to promote FMDV replication by inhibiting VISA-mediated innate immunity.Journal of virology · 2025Article
- Cerebral Cavernous Malformation: From Genetics to Pharmacotherapy.Brain and behavior · 2025Review
- Review
- Interplay analysis of lead exposure with key cardiovascular gene polymorphisms on blood pressure in a cross-sectional study of occupational workers.Scientific reports · 2024Article
- Article
- Role of Protein Phosphatases in Tumor Angiogenesis: Assessing PP1, PP2A, PP2B and PTPs Activity.International journal of molecular sciences · 2024Review
- Shear stress and pathophysiological PI3K involvement in vascular malformations.The Journal of clinical investigation · 2024Review
- Eph-ephrin signaling couples endothelial cell sorting and arterial specification.Nature communications · 2024Article
- Comprehensive CCM3 Mutational Analysis in Two Patients with Syndromic Cerebral Cavernous Malformation.Translational stroke research · 2024Article
- Role of Rho-Associated Kinase in the Pathophysiology of Cerebral Cavernous Malformations.Neurology. Genetics · 2024Review
- Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations.Journal of personalized medicine · 2023Review
- KRIT1: A Traffic Warden at the Busy Crossroads Between Redox Signaling and the Pathogenesis of Cerebral Cavernous Malformation Disease.Antioxidants & redox signaling · 2023Review
- Exosomal miR-30a-5p promoted intrahepatic cholangiocarcinoma progression by increasing angiogenesis and vascular permeability in PDCD10 dependent manner.International journal of biological sciences · 2023Article
- Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CCM3, a product of the cerebral cavernous malformation 3 or programmed cell death 10 gene (CCM3/PDCD10), is broadly expressed throughout development in both vertebrates and invertebrates. Increasing evidence indicates a crucial role of CCM3 in vascular development and in regulation of angiogenesis and apoptosis. Furthermore, loss of CCM3 causes inherited (familial) cerebral cavernous malformation (CCM), a common brain vascular anomaly involving aberrant angiogenesis. This study focused on signalling pathways underlying the angiogenic functions of CCM3. Silencing CCM3 by siRNA stimulated endothelial proliferation, migration and sprouting accompanied by significant downregulation of the core components of Notch signalling including DLL4, Notch4, HEY2 and HES1 and by activation of VEGF and Erk pathways. Treatment with recombinant DLL4 (rhDLL4) restored DLL4 expression and reversed CCM3-silence-mediated impairment of Notch signalling and reduced the ratio of VEGF-R2 to VEGF-R1 expression. Importantly, restoration of DLL4-Notch signalling entirely rescued the hyper-angiogenic phenotype induced by CCM3 silence. A concomitant loss of CCM3 and the core components of DLL4-Notch signalling were also demonstrated in CCM3-deficient endothelial cells derived from human CCM lesions (CCMEC) and in a CCM3 germline mutation carrier. This study defined DLL4 as a key downstream target of CCM3 in endothelial cells. CCM3/DLL4-Notch pathway serves as an important signalling for endothelial angiogenesis and is potentially implicated in the pathomechanism of human CCMs.
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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.