ArticleOncogene2011
c-Cbl inhibits angiogenesis and tumor growth by suppressing activation of PLCγ1.
Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- PTPN22 Dephosphorylates CBL to Inhibit PD-L1 Ubiquitination and Drive Immunosuppression in Renal Cell Carcinoma.International journal of biological sciences · 2026Article
- Cbl promotes MyD88 ubiquitin-mediated degradation in macrophages via phosphorylation and calcium mobilization.Frontiers in immunology · 2025Article
- Article
- Review
- E3 ligase c-Cbl regulates intestinal inflammation through suppressing fungi-induced noncanonical NF-κB activation.Science advances · 2021Article
- Cerebral arteriopathy associated with heterozygous variants in the casitas B-lineage lymphoma gene.Neurology. Genetics · 2020Article
- Haploinsufficiency of Casitas B-Lineage Lymphoma Augments the Progression of Colon Cancer in the Background of Adenomatous Polyposis Coli Inactivation.The American journal of pathology · 2020Article
- Review
- Pilot assessment of vascular endothelial growth factor receptors and trafficking pathways in recurrent and metastatic canine subcutaneous mast cell tumours.Veterinary medicine and science · 2017Article
- Mechanisms and regulation of endothelial VEGF receptor signalling.Nature reviews. Molecular cell biology · 2016Review
- The c-Cbl ubiquitin ligase regulates nuclear β-catenin and angiogenesis by its tyrosine phosphorylation mediated through the Wnt signaling pathway.The Journal of biological chemistry · 2015Article
- Set-based joint test of interaction between SNPs in the VEGF pathway and exogenous estrogen finds association with age-related macular degeneration.Investigative ophthalmology & visual science · 2014Article
- c-Cbl inhibition improves cardiac function and survival in response to myocardial ischemia.Circulation · 2014Article
- Identification of PDCL3 as a novel chaperone protein involved in the generation of functional VEGF receptor 2.The Journal of biological chemistry · 2013Article
- c-Cbl, a ubiquitin E3 ligase that targets active β-catenin: a novel layer of Wnt signaling regulation.The Journal of biological chemistry · 2013Article
- Regulation of VEGF signaling by membrane traffic.Cellular signalling · 2012Review
- Identification of IGPR-1 as a novel adhesion molecule involved in angiogenesis.Molecular biology of the cell · 2012Article
- The ubiquitin-proteasome system meets angiogenesis.Molecular cancer therapeutics · 2012Review
- PEST motif serine and tyrosine phosphorylation controls vascular endothelial growth factor receptor 2 stability and downregulation.Molecular and cellular biology · 2011Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Angiogenesis is regulated by highly coordinated function of various proteins with pro- and anti-angiogenic functions. Among the many cytoplasmic signaling proteins that are activated by VEGFR-2, activation of PLCγ1 is considered to have a pivotal role in angiogenic signaling. In previous study we have identified c-Cbl as a negative regulator of PLCγ1 in endothelial cells, the biochemical and biological significance of c-Cbl, however, in angiogenesis in vivo and molecular mechanisms involved were remained elusive. In this study, we report that genetic inactivation of c-Cbl in mice results in enhanced tumor angiogenesis and retinal neovascularization. Endothelial cells derived from c-Cbl null mice displayed elevated cell proliferation and tube formation in response to VEGF stimulation. Loss of c-Cbl also resulted in robust activation of PLCγ1 and increased intracellular calcium release. c-Cbl-dependent ubiquitination selectively inhibited tyrosine phosphorylation of PLCγ1 and mostly refrained from ubiquitin-mediated degradation. Hence, we propose c-Cbl as an angiogenic suppressor protein where upon activation it uniquely modulates PLCγ1 activation by ubiquitination and subsequently inhibits VEGF-driven angiogenesis.
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What OpenQuestion holds
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.