ArticleCell research2019
Endothelial CDS2 deficiency causes VEGFA-mediated vascular regression and tumor inhibition.
Article in Cell research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 58 citations in OpenAlex.
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- CDS2 expression regulates de novo phosphatidic acid synthesis.The Biochemical journal · 2024Article
- Noncaloric monosaccharides induce excessive sprouting angiogenesis in zebrafish via foxo1a-marcksl1a signal.eLife · 2024Article
- Neural progenitor-derived Apelin controls tip cell behavior and vascular patterning.Science advances · 2024Article
- Proteolytic activation of angiomotin by DDI2 promotes angiogenesis.The EMBO journal · 2023Article
- Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- The role of blood flow in vessel remodeling and its regulatory mechanism during developmental angiogenesis.Cellular and molecular life sciences : CMLS · 2023Review
- PI(4,5)PScience advances · 2023Article
- Identification and validation of a novel CD8+ T cell-associated prognostic model based on ferroptosis in acute myeloid leukemia.Frontiers in immunology · 2023Article
- Heterogeneities of zebrafish vasculature development studied by a high throughput light-sheet flow imaging system.Biomedical optics express · 2022Article
Corrections and comments
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Authors and funding
21 authors at 8 institutions in 2 countries.
Funding
Abstract
The response of endothelial cells to signaling stimulation is critical for vascular morphogenesis, homeostasis and function. Vascular endothelial growth factor-a (VEGFA) has been commonly recognized as a pro-angiogenic factor in vertebrate developmental, physiological and pathological conditions for decades. Here we report a novel finding that genetic ablation of CDP-diacylglycerol synthetase-2 (CDS2), a metabolic enzyme that controls phosphoinositide recycling, switches the output of VEGFA signaling from promoting angiogenesis to unexpectedly inducing vessel regression. Live imaging analysis uncovered the presence of reverse migration of the angiogenic endothelium in cds2 mutant zebrafish upon VEGFA stimulation, and endothelium regression also occurred in postnatal retina and implanted tumor models in mice. In tumor models, CDS2 deficiency enhanced the level of tumor-secreted VEGFA, which in-turn trapped tumors into a VEGFA-induced vessel regression situation, leading to suppression of tumor growth. Mechanistically, VEGFA stimulation reduced phosphatidylinositol (4,5)-bisphosphate (PIP2) availability in the absence of CDS2-controlled-phosphoinositide metabolism, subsequently causing phosphatidylinositol (3,4,5)-triphosphate (PIP3) deficiency and FOXO1 activation to trigger regression of CDS2-null endothelium. Thus, our data indicate that the effect of VEGFA on vasculature is context-dependent and can be converted from angiogenesis to vascular regression.
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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.