ArticleThe Journal of biological chemistry2013
The propeptides of VEGF-D determine heparin binding, receptor heterodimerization, and effects on tumor biology.
Article in The Journal of biological chemistry, 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, 27 citations in OpenAlex.
- Beyond vessels: unraveling the impact of VEGFs on neuronal functions and structure.Journal of biomedical science · 2025Review
- Extracellular vesicle-bound VEGF in oral squamous cell carcinoma and its role in resistance to Bevacizumab Therapy.Cancer cell international · 2024Article
- Vascular Endothelial Growth Factor-D (VEGF-D): An Angiogenesis Bypass in Malignant Tumors.International journal of molecular sciences · 2023Review
- GSEA-SDBE: A gene selection method for breast cancer classification based on GSEA and analyzing differences in performance metrics.PloS one · 2022Article
- Heparanase and the hallmarks of cancer.Journal of translational medicine · 2020Review
- Molecular background of the regional lymph node metastasis of gastric cancer.Oncology letters · 2018Review
- Emerging Roles for VEGF-D in Human Disease.Biomolecules · 2018Review
- Pulmonary Vasculopathy Associated with FIGF Gene Mutation.The American journal of pathology · 2017Article
- Differential Receptor Binding and Regulatory Mechanisms for the Lymphangiogenic Growth Factors Vascular Endothelial Growth Factor (VEGF)-C and -D.The Journal of biological chemistry · 2016Article
- Sulfatase 2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D.Oncology reports · 2016Article
- Sulfatase 2 promotes breast cancer progression through regulating some tumor-related factors.Oncology reports · 2016Article
- The relevance of cell type- and tumor zone-specific VEGFR-2 activation in locally advanced colon cancer.Journal of experimental & clinical cancer research : CR · 2015Article
- Structural basis for VEGF-C binding to neuropilin-2 and sequestration by a soluble splice form.Structure (London, England : 1993) · 2015Article
- Heparan sulfate signaling in cancer.Trends in biochemical sciences · 2014Review
- Pulmonary lymphangiectasia resulting from vascular endothelial growth factor-C overexpression during a critical period.Circulation research · 2014Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
VEGF-D is an angiogenic and lymphangiogenic glycoprotein that can be proteolytically processed generating various forms differing in subunit composition due to the presence or absence of N- and C-terminal propeptides. These propeptides flank the central VEGF homology domain, that contains the binding sites for VEGF receptors (VEGFRs), but their biological functions were unclear. Characterization of propeptide function will be important to clarify which forms of VEGF-D are biologically active and therefore clinically relevant. Here we use VEGF-D mutants deficient in either propeptide, and in the capacity to process the remaining propeptide, to monitor the functions of these domains. We report for the first time that VEGF-D binds heparin, and that the C-terminal propeptide significantly enhances this interaction (removal of this propeptide from full-length VEGF-D completely prevents heparin binding). We also show that removal of either the N- or C-terminal propeptide is required for VEGF-D to drive formation of VEGFR-2/VEGFR-3 heterodimers which have recently been shown to positively regulate angiogenic sprouting. The mature form of VEGF-D, lacking both propeptides, can also promote formation of these receptor heterodimers. In a mouse tumor model, removal of only the C-terminal propeptide from full-length VEGF-D was sufficient to enhance angiogenesis and tumor growth. In contrast, removal of both propeptides is required for high rates of lymph node metastasis. The findings reported here show that the propeptides profoundly influence molecular interactions of VEGF-D with VEGF receptors, co-receptors, and heparin, and its effects on tumor biology.
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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.