Browse VEGFA

Summary
SymbolVEGFA
Namevascular endothelial growth factor A
Aliases VEGF-A; VPF; VEGF; vascular endothelial growth factor; MVCD1; vascular permeability factor
Chromosomal Location6p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Secreted Note=VEGF121 is acidic and freely secreted. VEGF165 is more basic, has heparin-binding properties and, although a signicant proportion remains cell-associated, most is freely secreted. VEGF189 is very basic, it is cell-associated after secretion and is bound avidly by heparin and the extracellular matrix, although it may be released as a soluble form by heparin, heparinase or plasmin.
Domain PF00341 PDGF/VEGF domain
PF14554 VEGF heparin-binding domain
Function

Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth. Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (By similarity).

> Gene Ontology
 
Biological Process GO:0001525 angiogenesis
GO:0001541 ovarian follicle development
GO:0001558 regulation of cell growth
GO:0001569 patterning of blood vessels
GO:0001570 vasculogenesis
GO:0001654 eye development
GO:0001655 urogenital system development
GO:0001657 ureteric bud development
GO:0001658 branching involved in ureteric bud morphogenesis
GO:0001666 response to hypoxia
GO:0001667 ameboidal-type cell migration
GO:0001701 in utero embryonic development
GO:0001754 eye photoreceptor cell differentiation
GO:0001763 morphogenesis of a branching structure
GO:0001822 kidney development
GO:0001823 mesonephros development
GO:0001894 tissue homeostasis
GO:0001935 endothelial cell proliferation
GO:0001936 regulation of endothelial cell proliferation
GO:0001938 positive regulation of endothelial cell proliferation
GO:0001945 lymph vessel development
GO:0001952 regulation of cell-matrix adhesion
GO:0001954 positive regulation of cell-matrix adhesion
GO:0002040 sprouting angiogenesis
GO:0002042 cell migration involved in sprouting angiogenesis
GO:0002052 positive regulation of neuroblast proliferation
GO:0002053 positive regulation of mesenchymal cell proliferation
GO:0002090 regulation of receptor internalization
GO:0002092 positive regulation of receptor internalization
GO:0002262 myeloid cell homeostasis
GO:0002521 leukocyte differentiation
GO:0002573 myeloid leukocyte differentiation
GO:0002576 platelet degranulation
GO:0002685 regulation of leukocyte migration
GO:0002687 positive regulation of leukocyte migration
GO:0003007 heart morphogenesis
GO:0003151 outflow tract morphogenesis
GO:0003169 coronary vein morphogenesis
GO:0006140 regulation of nucleotide metabolic process
GO:0006476 protein deacetylation
GO:0006887 exocytosis
GO:0006898 receptor-mediated endocytosis
GO:0007044 cell-substrate junction assembly
GO:0007045 cell-substrate adherens junction assembly
GO:0007160 cell-matrix adhesion
GO:0007389 pattern specification process
GO:0007405 neuroblast proliferation
GO:0007409 axonogenesis
GO:0007411 axon guidance
GO:0007423 sensory organ development
GO:0007498 mesoderm development
GO:0007507 heart development
GO:0007548 sex differentiation
GO:0007589 body fluid secretion
GO:0007595 lactation
GO:0008360 regulation of cell shape
GO:0008361 regulation of cell size
GO:0008406 gonad development
GO:0008585 female gonad development
GO:0009150 purine ribonucleotide metabolic process
GO:0009187 cyclic nucleotide metabolic process
GO:0009791 post-embryonic development
GO:0010463 mesenchymal cell proliferation
GO:0010464 regulation of mesenchymal cell proliferation
GO:0010466 negative regulation of peptidase activity
GO:0010594 regulation of endothelial cell migration
GO:0010595 positive regulation of endothelial cell migration
GO:0010631 epithelial cell migration
GO:0010632 regulation of epithelial cell migration
GO:0010634 positive regulation of epithelial cell migration
GO:0010720 positive regulation of cell development
GO:0010769 regulation of cell morphogenesis involved in differentiation
GO:0010770 positive regulation of cell morphogenesis involved in differentiation
GO:0010810 regulation of cell-substrate adhesion
GO:0010811 positive regulation of cell-substrate adhesion
GO:0010951 negative regulation of endopeptidase activity
GO:0010975 regulation of neuron projection development
GO:0010976 positive regulation of neuron projection development
GO:0014706 striated muscle tissue development
GO:0016049 cell growth
GO:0016570 histone modification
GO:0016575 histone deacetylation
GO:0018105 peptidyl-serine phosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018209 peptidyl-serine modification
GO:0018212 peptidyl-tyrosine modification
GO:0021700 developmental maturation
GO:0022602 ovulation cycle process
GO:0022604 regulation of cell morphogenesis
GO:0030099 myeloid cell differentiation
GO:0030100 regulation of endocytosis
GO:0030218 erythrocyte differentiation
GO:0030224 monocyte differentiation
GO:0030225 macrophage differentiation
GO:0030307 positive regulation of cell growth
GO:0030323 respiratory tube development
GO:0030324 lung development
GO:0030335 positive regulation of cell migration
GO:0030516 regulation of axon extension
GO:0030799 regulation of cyclic nucleotide metabolic process
GO:0030823 regulation of cGMP metabolic process
GO:0030879 mammary gland development
GO:0030947 regulation of vascular endothelial growth factor receptor signaling pathway
GO:0030949 positive regulation of vascular endothelial growth factor receptor signaling pathway
GO:0031056 regulation of histone modification
GO:0031058 positive regulation of histone modification
GO:0031063 regulation of histone deacetylation
GO:0031065 positive regulation of histone deacetylation
GO:0031077 post-embryonic camera-type eye development
GO:0031098 stress-activated protein kinase signaling cascade
GO:0031290 retinal ganglion cell axon guidance
GO:0031334 positive regulation of protein complex assembly
GO:0031346 positive regulation of cell projection organization
GO:0031589 cell-substrate adhesion
GO:0031623 receptor internalization
GO:0031952 regulation of protein autophosphorylation
GO:0031954 positive regulation of protein autophosphorylation
GO:0032103 positive regulation of response to external stimulus
GO:0032147 activation of protein kinase activity
GO:0032535 regulation of cellular component size
GO:0032793 positive regulation of CREB transcription factor activity
GO:0032872 regulation of stress-activated MAPK cascade
GO:0032874 positive regulation of stress-activated MAPK cascade
GO:0032941 secretion by tissue
GO:0033135 regulation of peptidyl-serine phosphorylation
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0033674 positive regulation of kinase activity
GO:0034101 erythrocyte homeostasis
GO:0034329 cell junction assembly
GO:0034330 cell junction organization
GO:0034332 adherens junction organization
GO:0034333 adherens junction assembly
GO:0035051 cardiocyte differentiation
GO:0035148 tube formation
GO:0035162 embryonic hemopoiesis
GO:0035239 tube morphogenesis
GO:0035601 protein deacylation
GO:0035767 endothelial cell chemotaxis
GO:0035886 vascular smooth muscle cell differentiation
GO:0035924 cellular response to vascular endothelial growth factor stimulus
GO:0036003 positive regulation of transcription from RNA polymerase II promoter in response to stress
GO:0036293 response to decreased oxygen levels
GO:0036294 cellular response to decreased oxygen levels
GO:0036303 lymph vessel morphogenesis
GO:0038033 positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway
GO:0038066 p38MAPK cascade
GO:0038083 peptidyl-tyrosine autophosphorylation
GO:0038084 vascular endothelial growth factor signaling pathway
GO:0038086 VEGF-activated platelet-derived growth factor receptor signaling pathway
GO:0038089 positive regulation of cell migration by vascular endothelial growth factor signaling pathway
GO:0038091 positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway
GO:0038189 neuropilin signaling pathway
GO:0038190 VEGF-activated neuropilin signaling pathway
GO:0040017 positive regulation of locomotion
GO:0042461 photoreceptor cell development
GO:0042462 eye photoreceptor cell development
GO:0042692 muscle cell differentiation
GO:0042698 ovulation cycle
GO:0043010 camera-type eye development
GO:0043112 receptor metabolic process
GO:0043129 surfactant homeostasis
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043254 regulation of protein complex assembly
GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043405 regulation of MAP kinase activity
GO:0043406 positive regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0043534 blood vessel endothelial cell migration
GO:0043535 regulation of blood vessel endothelial cell migration
GO:0043536 positive regulation of blood vessel endothelial cell migration
GO:0043542 endothelial cell migration
GO:0043618 regulation of transcription from RNA polymerase II promoter in response to stress
GO:0043620 regulation of DNA-templated transcription in response to stress
GO:0044089 positive regulation of cellular component biogenesis
GO:0045055 regulated exocytosis
GO:0045137 development of primary sexual characteristics
GO:0045216 cell-cell junction organization
GO:0045666 positive regulation of neuron differentiation
GO:0045765 regulation of angiogenesis
GO:0045766 positive regulation of angiogenesis
GO:0045773 positive regulation of axon extension
GO:0045785 positive regulation of cell adhesion
GO:0045807 positive regulation of endocytosis
GO:0045860 positive regulation of protein kinase activity
GO:0045861 negative regulation of proteolysis
GO:0045927 positive regulation of growth
GO:0046068 cGMP metabolic process
GO:0046530 photoreceptor cell differentiation
GO:0046545 development of primary female sexual characteristics
GO:0046660 female sex differentiation
GO:0046777 protein autophosphorylation
GO:0048008 platelet-derived growth factor receptor signaling pathway
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0048041 focal adhesion assembly
GO:0048259 regulation of receptor-mediated endocytosis
GO:0048260 positive regulation of receptor-mediated endocytosis
GO:0048469 cell maturation
GO:0048511 rhythmic process
GO:0048514 blood vessel morphogenesis
GO:0048568 embryonic organ development
GO:0048569 post-embryonic animal organ development
GO:0048588 developmental cell growth
GO:0048592 eye morphogenesis
GO:0048593 camera-type eye morphogenesis
GO:0048608 reproductive structure development
GO:0048638 regulation of developmental growth
GO:0048639 positive regulation of developmental growth
GO:0048667 cell morphogenesis involved in neuron differentiation
GO:0048675 axon extension
GO:0048732 gland development
GO:0048738 cardiac muscle tissue development
GO:0048739 cardiac muscle fiber development
GO:0048747 muscle fiber development
GO:0048754 branching morphogenesis of an epithelial tube
GO:0048841 regulation of axon extension involved in axon guidance
GO:0048842 positive regulation of axon extension involved in axon guidance
GO:0048844 artery morphogenesis
GO:0048845 venous blood vessel morphogenesis
GO:0048846 axon extension involved in axon guidance
GO:0048871 multicellular organismal homeostasis
GO:0048872 homeostasis of number of cells
GO:0048875 chemical homeostasis within a tissue
GO:0050673 epithelial cell proliferation
GO:0050678 regulation of epithelial cell proliferation
GO:0050679 positive regulation of epithelial cell proliferation
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050769 positive regulation of neurogenesis
GO:0050770 regulation of axonogenesis
GO:0050772 positive regulation of axonogenesis
GO:0050878 regulation of body fluid levels
GO:0050900 leukocyte migration
GO:0050918 positive chemotaxis
GO:0050920 regulation of chemotaxis
GO:0050921 positive regulation of chemotaxis
GO:0050926 regulation of positive chemotaxis
GO:0050927 positive regulation of positive chemotaxis
GO:0050930 induction of positive chemotaxis
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051145 smooth muscle cell differentiation
GO:0051146 striated muscle cell differentiation
GO:0051272 positive regulation of cellular component movement
GO:0051302 regulation of cell division
GO:0051346 negative regulation of hydrolase activity
GO:0051403 stress-activated MAPK cascade
GO:0051781 positive regulation of cell division
GO:0051893 regulation of focal adhesion assembly
GO:0051894 positive regulation of focal adhesion assembly
GO:0051962 positive regulation of nervous system development
GO:0052547 regulation of peptidase activity
GO:0052548 regulation of endopeptidase activity
GO:0055001 muscle cell development
GO:0055002 striated muscle cell development
GO:0055006 cardiac cell development
GO:0055007 cardiac muscle cell differentiation
GO:0055013 cardiac muscle cell development
GO:0060215 primitive hemopoiesis
GO:0060249 anatomical structure homeostasis
GO:0060319 primitive erythrocyte differentiation
GO:0060326 cell chemotaxis
GO:0060537 muscle tissue development
GO:0060541 respiratory system development
GO:0060560 developmental growth involved in morphogenesis
GO:0060562 epithelial tube morphogenesis
GO:0060627 regulation of vesicle-mediated transport
GO:0060675 ureteric bud morphogenesis
GO:0060688 regulation of morphogenesis of a branching structure
GO:0060749 mammary gland alveolus development
GO:0060840 artery development
GO:0060841 venous blood vessel development
GO:0060947 cardiac vascular smooth muscle cell differentiation
GO:0060948 cardiac vascular smooth muscle cell development
GO:0060976 coronary vasculature development
GO:0060977 coronary vasculature morphogenesis
GO:0060982 coronary artery morphogenesis
GO:0060993 kidney morphogenesis
GO:0061138 morphogenesis of a branching epithelium
GO:0061213 positive regulation of mesonephros development
GO:0061217 regulation of mesonephros development
GO:0061326 renal tubule development
GO:0061333 renal tubule morphogenesis
GO:0061351 neural precursor cell proliferation
GO:0061377 mammary gland lobule development
GO:0061387 regulation of extent of cell growth
GO:0061418 regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0061419 positive regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0061458 reproductive system development
GO:0061564 axon development
GO:0070302 regulation of stress-activated protein kinase signaling cascade
GO:0070304 positive regulation of stress-activated protein kinase signaling cascade
GO:0070482 response to oxygen levels
GO:0070528 protein kinase C signaling
GO:0071453 cellular response to oxygen levels
GO:0071456 cellular response to hypoxia
GO:0071542 dopaminergic neuron differentiation
GO:0071679 commissural neuron axon guidance
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0072001 renal system development
GO:0072006 nephron development
GO:0072009 nephron epithelium development
GO:0072028 nephron morphogenesis
GO:0072073 kidney epithelium development
GO:0072078 nephron tubule morphogenesis
GO:0072080 nephron tubule development
GO:0072088 nephron epithelium morphogenesis
GO:0072089 stem cell proliferation
GO:0072091 regulation of stem cell proliferation
GO:0072163 mesonephric epithelium development
GO:0072164 mesonephric tubule development
GO:0072171 mesonephric tubule morphogenesis
GO:0089700 protein kinase D signaling
GO:0090036 regulation of protein kinase C signaling
GO:0090037 positive regulation of protein kinase C signaling
GO:0090045 positive regulation of deacetylase activity
GO:0090049 regulation of cell migration involved in sprouting angiogenesis
GO:0090050 positive regulation of cell migration involved in sprouting angiogenesis
GO:0090066 regulation of anatomical structure size
GO:0090109 regulation of cell-substrate junction assembly
GO:0090130 tissue migration
GO:0090132 epithelium migration
GO:0090183 regulation of kidney development
GO:0090184 positive regulation of kidney development
GO:0090189 regulation of branching involved in ureteric bud morphogenesis
GO:0090190 positive regulation of branching involved in ureteric bud morphogenesis
GO:0090259 regulation of retinal ganglion cell axon guidance
GO:0090287 regulation of cellular response to growth factor stimulus
GO:0090311 regulation of protein deacetylation
GO:0090312 positive regulation of protein deacetylation
GO:0090596 sensory organ morphogenesis
GO:0097084 vascular smooth muscle cell development
GO:0097485 neuron projection guidance
GO:0098732 macromolecule deacylation
GO:1900084 regulation of peptidyl-tyrosine autophosphorylation
GO:1900086 positive regulation of peptidyl-tyrosine autophosphorylation
GO:1900542 regulation of purine nucleotide metabolic process
GO:1900744 regulation of p38MAPK cascade
GO:1900745 positive regulation of p38MAPK cascade
GO:1901342 regulation of vasculature development
GO:1901522 positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus
GO:1901725 regulation of histone deacetylase activity
GO:1901727 positive regulation of histone deacetylase activity
GO:1901888 regulation of cell junction assembly
GO:1901890 positive regulation of cell junction assembly
GO:1902275 regulation of chromatin organization
GO:1902284 neuron projection extension involved in neuron projection guidance
GO:1902336 positive regulation of retinal ganglion cell axon guidance
GO:1902667 regulation of axon guidance
GO:1902669 positive regulation of axon guidance
GO:1902692 regulation of neuroblast proliferation
GO:1903131 mononuclear cell differentiation
GO:1903391 regulation of adherens junction organization
GO:1903393 positive regulation of adherens junction organization
GO:1903570 regulation of protein kinase D signaling
GO:1903572 positive regulation of protein kinase D signaling
GO:1903670 regulation of sprouting angiogenesis
GO:1903672 positive regulation of sprouting angiogenesis
GO:1904018 positive regulation of vasculature development
GO:1905269 positive regulation of chromatin organization
GO:1905330 regulation of morphogenesis of an epithelium
GO:1905332 positive regulation of morphogenesis of an epithelium
GO:1990138 neuron projection extension
GO:2000027 regulation of organ morphogenesis
GO:2000116 regulation of cysteine-type endopeptidase activity
GO:2000117 negative regulation of cysteine-type endopeptidase activity
GO:2000147 positive regulation of cell motility
GO:2000177 regulation of neural precursor cell proliferation
GO:2000179 positive regulation of neural precursor cell proliferation
GO:2000648 positive regulation of stem cell proliferation
GO:2001026 regulation of endothelial cell chemotaxis
GO:2001028 positive regulation of endothelial cell chemotaxis
Molecular Function GO:0001968 fibronectin binding
GO:0005125 cytokine activity
GO:0005126 cytokine receptor binding
GO:0005161 platelet-derived growth factor receptor binding
GO:0005172 vascular endothelial growth factor receptor binding
GO:0005539 glycosaminoglycan binding
GO:0008083 growth factor activity
GO:0008201 heparin binding
GO:0030545 receptor regulator activity
GO:0030546 receptor activator activity
GO:0042056 chemoattractant activity
GO:0043183 vascular endothelial growth factor receptor 1 binding
GO:0043184 vascular endothelial growth factor receptor 2 binding
GO:0046982 protein heterodimerization activity
GO:0048018 receptor agonist activity
GO:0050840 extracellular matrix binding
GO:0070851 growth factor receptor binding
GO:1901681 sulfur compound binding
Cellular Component GO:0005578 proteinaceous extracellular matrix
GO:0030141 secretory granule
GO:0031091 platelet alpha granule
GO:0031093 platelet alpha granule lumen
GO:0031983 vesicle lumen
GO:0034774 secretory granule lumen
GO:0060205 cytoplasmic membrane-bounded vesicle lumen
GO:0099503 secretory vesicle
> KEGG and Reactome Pathway
 
KEGG hsa04014 Ras signaling pathway
hsa04015 Rap1 signaling pathway
hsa04060 Cytokine-cytokine receptor interaction
hsa04066 HIF-1 signaling pathway
hsa04151 PI3K-Akt signaling pathway
hsa04370 VEGF signaling pathway
hsa04510 Focal adhesion
Reactome R-HSA-422475: Axon guidance
R-HSA-2262749: Cellular response to hypoxia
R-HSA-2262752: Cellular responses to stress
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-1266738: Developmental Biology
R-HSA-2682334: EPH-Ephrin signaling
R-HSA-3928663: EPHA-mediated growth cone collapse
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-114608: Platelet degranulation
R-HSA-1234174: Regulation of Hypoxia-inducible Factor (HIF) by oxygen
R-HSA-1234158: Regulation of gene expression by Hypoxia-inducible Factor
R-HSA-76005: Response to elevated platelet cytosolic Ca2+
R-HSA-162582: Signal Transduction
R-HSA-449147: Signaling by Interleukins
R-HSA-194138: Signaling by VEGF
R-HSA-8866910: TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
R-HSA-8864260: Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors
R-HSA-195399: VEGF binds to VEGFR leading to receptor dimerization
R-HSA-194313: VEGF ligand-receptor interactions
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-5218921: VEGFR2 mediated cell proliferation
Summary
SymbolVEGFA
Namevascular endothelial growth factor A
Aliases VEGF-A; VPF; VEGF; vascular endothelial growth factor; MVCD1; vascular permeability factor
Chromosomal Location6p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between VEGFA and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between VEGFA and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
27076627Ovarian CarcinomaInhibit immunity (NKT cell function)We found that VEGF inhibition restores NKT-cell function in an in vitro ovarian cancer model.
25601652Colon CarcinomaInhibit immunity (T cell function)We report in the present work that VEGF-A produced in the tumor microenvironment enhances expression of PD-1 and other inhibitory checkpoints involved in CD8(+) T cell exhaustion, which could be reverted by anti-angiogenic agents targeting VEGF-A-VEGFR.
25589622E7+ tumor TC-1Inhibit immunity (T cell function)Gain of HIF-1α under normoxia in cancer mediates immune adaptation through the AKT/ERK and VEGFA axes. We found that tumor cells gain HIF-1α in the course of immune selection under normoxia and that HIF-1α renders tumor cells resistant to lysis by tumor-specific cytotoxic T lymphocytes (CTL) in culture and in mice.
22529296MelanomaInhibit immunity (T cell function)These data suggest a critical role for tumor-expressed iNOS in the recruitment and induction of functional MDSC by modulation of tumor VEGF secretion and upregulation of STAT3 and ROS in MDSC.
18381453Renal Cell CarcinomaInhibit immunity (T cell function); immunotherapy targetIn the future, T cells directed against VEGF as a tumor-associated antigen may represent a possible way of combining peptide-based anti-VEGF immunotherapy with already existent anti-VEGF cancer therapies.
27286797GilomaInhibit immunity (T cell function)Here we explore whether the TGF-β pathway, which promotes angiogenesis, invasiveness, and immunosuppression, acts as an escape pathway from VEGF inhibition. Our study highlights the biological heterogeneity of murine glioma models and illustrates that cotargeting of the VEGF and TGF-β pathways might lead to improved tumor control only in subsets of glioblastoma.
19240164MelanomaInhibit immunityThese data support prior observations regarding the effect of VEGF on immune cell function and suggests consideration of VEGF inhibitors in future cancer immunotherapy clinical studies in metastatic melanoma.
23514705Pancreatic CarcinomaInhibit immunity (T cell function)Luminex analysis indicated that PSC but not human fetal primary pancreatic fibroblast cells (HPF; negative controls) produced MDSC-promoting cytokines [interleukin (IL-6), VEGF, macrophage colony-stimulating factor (M-CSF) ] and chemokines (SDF-1, MCP-1).
23447383Chronic Lymphocytic LeukemiaInhibit immunity (T cell function)In our study, we characterized mRNA levels of VEGF receptors including NRP1 in a large cohort of CLL patients (n = 114), additionally we performed a detailed characterization of NRP1 expression on B cells, plasmacytoid dendritic cells (PDCs) and regulatory T cells (Tregs). The expression of NRP1 was significantly higher on leukemic lymphocytes compared to control B lymphocytes on mRNA and protein levels (22.72% vs. 0.2%, p = 0.0003, respectively), Tregs (42.6% vs. 16.05%, p = 0.0003) and PDCs (100% vs. 98% p < 0.0001). In functional studies, we found higher NRP1 expression on CLL cells after stimulation with VEGF. The correlation between expression of VEGF receptors: FLT1, NRP1 and FOXP3 expression (r(2) = 0.53, p < 0.0001 and r(2) = 0.49, p < 0.0001, respectively) was observed.
21209070Colon CarcinomaInhibit immunity (T cell function)Antagonism of VEGF by genetically engineered dendritic cells is essential to induce antitumor immunity against malignant ascites. Using a murine model of MA with CT26 colon cancer cells, we here determined that the imbalance between the VEGF-A/vascular permeability factor and its decoy receptor, soluble fms-like tryrosine kinase receptor-1 (sFLT-1), was a major cause of MA resistance to dendritic cell (DC)-based immunotherapy. These findings were not seen in immunodeficient mice, indicating that a VEGF-A/sFLT-1 imbalance is critical for determining the antitumor immune response by DC-vaccination therapy against MA.
21159663MelanomaInhibit immunityInduction of monocyte chemoattractant protein-1 and interleukin-10 by TGFbeta1 in melanoma enhances tumor infiltration and immunosuppression. Supernatants from TGFβ1-treated A375 cells enhanced MCP-1-dependent migration of monocytes, which, in turn, expressed high levels of TGF,β1, bFGF, and VEGF mRNA.
29034589Colon CarcinomaInhibit immunity (T cell function)Giving angiotensin II receptor blockers (ARB) to C57BL/6 mice bearing murine colon cancer cell line MC38 resulted in significant enhancement of tumor antigen gp70 specific T cells. ARB administration did not change the numbers of CD11b+ myeloid cells in tumors, but significantly reduced their T-cell inhibitory ability along with decreased production of various immunosuppressive factors including interleukin (IL)-6, IL-10, vascular endothelial growth factor (VEGF), and arginase by CD11b+ cells in tumors.
24778130Clear Cell Renal Cell CarcinomaInhibit immunity (infiltration)In addition, there was a significant and positive relationship between the presence of TIL as assessed by IHC for CD3 and PDL-1 by IHC (r = 0.25; P = 0.015), and there was a trend toward an inverse relationship between TIL and VEGFA gene expression (r = -0.18; P = 0.089).
20822802Ovarian CarcinomaInhibit immunityThese antibodies were shown to inhibit ovarian cancer xenograft growth in a nude mouse model following intraperitoneal passive immunization. Active immunization with the VEGF peptide vaccine inhibited VEGF-dependent pancreatic islet cell tumor growth in RIP1-Tag2 transgenic mice and was associated with decreased vasculogenesis in these tumors compared with animals vaccinated with an irrelevant peptide. Active immunization also inhibited growth of tumors from a VEGF overexpressing ovarian cancer cell line, resulting in decreased tumor size and tumor vessel density compared with control mice
19201693Renal Cell CarcinomaInhibit immunity (T cell function)Treatment of RCC patients with anti-VEGF antibody bevacizumab, however, did not reduce the accumulation of MDSC in peripheral blood. In contrast, the addition of interleukin-2 to the treatment increased the number of MDSC in peripheral blood and the plasma levels of arginase I.
24938283postsurgical lung metastasis, fibrosarcomaInhibit immunity (T cell function); immunotherapy targetUnderscoring the potency of stroma-targeted costimulation and the broad spectrum of tumors secreting VEGF, in preclinical murine tumor models, systemic administration of the VEGF-targeted 4-1BB aptamer conjugates engendered potent antitumor immunity against multiple unrelated tumors in subcutaneous, postsurgical lung metastasis, methylcholantrene-induced fibrosarcoma, and oncogene-induced autochthonous glioma models, and exhibited a superior therapeutic index compared with nontargeted administration of an agonistic 4-1BB Ab or 4-1BB aptamer.
29686284Prostate CarcinomaInhibit immunityCP1 also decreases intra-tumoral regulatory T cells and VEGF.
29666026Cervical CarcinomaInhibit immunity (T cell function)Vascular endothelial growth factor Vascular endothelial growth factor (VEGF) has emerged as a therapeutic target in several malignancies, including cervical cancer.
29656749lung adenocarcinomaInhibit immunityTAMs had high expression of Tgf-β, Vegf, Fgf2, Fgf10, Fgfr2 and several matrix metalloproteinases; factors that play multiple roles in supporting tumor growth, immune protection, fibroblast activation and angiogenesis.
29619980lung adenocarcinomaInhibit immunityThrough the downregulation of vascular endothelial growth factor (VEGF), AHFRT inhibited VEGF/VEGF receptor signaling, which was essential for MDSC recruitment.
21298574Ovarian CancinomaInhibit immunityWe will discuss the role of angiogenesis and the tumor endothelium on regulation of the antitumor immune response with a special emphasis on the role of vascular endothelial growth factor (VEGF) in the suppression of immunological processes, which control tumor progression and its unique crosstalk with endothelin systems, and how their interactions may shape the antitumor immune response.
20144842Ovarian CancinomaInhibit immunityFurthermore, vascular endothelial growth factor (VEGF) is also known to have an immune-suppressing role besides its angiogenic role.
29215754Head and Neck Squamous Cell CarcinomaInhibit immunityMoreover, in HNSCC transgenic mouse model, inhibiting JAK2/STAT3 not only suppressed angiogenesis but also reduced MDSCs in the tumor microenvironment through suppressing VEGFA and CK2.
29136509Breast CarcinomaInhibit immunityAnalyses of human breast cancer showed inverse correlations between VEGF-A expression and CD8+T cell infiltration, and a link between T cell infiltration and vascularization.
28899975ChoriocarcinomaInhibit immunityWe recently identified endocrine gland-derived vascular endothelial growth factor (EG-VEGF) as a novel key placental growth factor that controls trophoblast proliferation and invasion. Treatment of the animal model with EG-VEGF receptor's antagonists significantly reduced tumor development and progression and preserved pregnancy.
20631075MelanomaInhibit immunity; Resistant to immunotherapyThe administration of an antibody against mouse VEGF synergized with ACT to enhance inhibition of established, vascularized, B16 melanoma (P = 0.009) and improve survival (P = 0.003). Thus, normalization of tumor vasculature through disruption of the VEGF/VEGFR-2 axis can increase extravasation of adoptively transferred T cells into the tumor and improve ACT-based immunotherapy.
21969559MelanomaInhibit immunityIndeed, upon manipulation of the melanoma microenvironment with the phosphodiesterase-5 inhibitor sildenafil, we observed reduced levels of numerous inflammatory mediators (e.g., IL-1β, IL-6, VEGF, S100A9) in association with decreased MDSC amounts and immunosuppressive function, indicating an antiinflammatory effect of sildenafil
21825014Lung CarcinomaInhibit immunityHere, we report a novel mechanism of escape from T-cell immunity that is caused by reduction in levels of the Delta family Notch ligands DLL1 and DLL4 in hematopoietic microenvironments. An important mediator of this effect was an elevation in the levels of circulating VEGF. Selective activation of the DLL1-Notch signaling pathway in bone marrow precursors enhanced T-cell activation and inhibited tumor growth.
16801397MelanomaInhibit immunityHere, we demonstrate a novel role of the activated MAPK pathway in immune evasion by melanoma cells with the mutation of BRAF, which encodes a MAPKKs, (BRAF(V600E)). MEK inhibitor U0126 or RNA interference (RNAi) for BRAF(V600E) decreased production of the immunosuppressive soluble factors interleukin (IL)-10, VEGF, or IL-6 from melanoma cells to levels comparable to those after signal transducer and activator of transcription (STAT)3 inactivation
Summary
SymbolVEGFA
Namevascular endothelial growth factor A
Aliases VEGF-A; VPF; VEGF; vascular endothelial growth factor; MVCD1; vascular permeability factor
Chromosomal Location6p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of VEGFA in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolVEGFA
Namevascular endothelial growth factor A
Aliases VEGF-A; VPF; VEGF; vascular endothelial growth factor; MVCD1; vascular permeability factor
Chromosomal Location6p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of VEGFA in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.7710.0764
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-1.3660.494
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.3290.813
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.3870.335
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.1990.94
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.6170.862
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.050.93
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.0580.975
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0320.986
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.3130.908
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.870.626
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0960.502
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of VEGFA in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.703.70.27
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916012.5-12.50.52
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47014.3-14.31
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11139.109.10.458
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 6116.7016.71
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolVEGFA
Namevascular endothelial growth factor A
Aliases VEGF-A; VPF; VEGF; vascular endothelial growth factor; MVCD1; vascular permeability factor
Chromosomal Location6p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of VEGFA. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolVEGFA
Namevascular endothelial growth factor A
Aliases VEGF-A; VPF; VEGF; vascular endothelial growth factor; MVCD1; vascular permeability factor
Chromosomal Location6p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of VEGFA. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by VEGFA.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolVEGFA
Namevascular endothelial growth factor A
Aliases VEGF-A; VPF; VEGF; vascular endothelial growth factor; MVCD1; vascular permeability factor
Chromosomal Location6p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of VEGFA. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolVEGFA
Namevascular endothelial growth factor A
Aliases VEGF-A; VPF; VEGF; vascular endothelial growth factor; MVCD1; vascular permeability factor
Chromosomal Location6p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of VEGFA expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolVEGFA
Namevascular endothelial growth factor A
Aliases VEGF-A; VPF; VEGF; vascular endothelial growth factor; MVCD1; vascular permeability factor
Chromosomal Location6p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between VEGFA and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolVEGFA
Namevascular endothelial growth factor A
Aliases VEGF-A; VPF; VEGF; vascular endothelial growth factor; MVCD1; vascular permeability factor
Chromosomal Location6p12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting VEGFA collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting VEGFA.
ID Name Drug Type Targets #Targets
DB00112BevacizumabBiotechC1QA, C1QB, C1QC, C1R, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A, FCG ......11
DB01017MinocyclineSmall MoleculeALOX5, CASP1, CASP3, CYCS, IL1B, MMP9, VEGFA7
DB01120GliclazideSmall MoleculeABCC8, VEGFA2
DB01136CarvedilolSmall MoleculeADRA1A, ADRA1B, ADRA1D, ADRA2A, ADRA2B, ADRA2C, ADRB1, ADRB2, GJA1 ......17
DB01270RanibizumabBiotechVEGFA1
DB03088Pidolic AcidSmall MoleculeADAM28, AMY1A, AMY2A, AMY2B, ANG, CCL8, HCRT, KRTAP5-2, TFF2, VEGF ......10
DB03754TromethamineSmall MoleculeAMD1, CANT1, DCN, NEIL1, VEGFA5
DB05294VandetanibSmall MoleculeEGFR, PTK6, RET, TEK, VEGFA5
DB05434ABT-510Small MoleculeCXCL8, FGF2, HGF, VEGFA4
DB05890VEGF-ASSmall MoleculeVEGFA1
DB05932DenibulinSmall MoleculeFLT1, FLT4, VEGFA3
DB05969SNS-032Small MoleculeCDK7, VEGFA2
DB06642BevasiranibBiotechVEGFA1
DB06779DalteparinSmall MoleculeSELP, SERPINC1, TFPI, VEGFA4
DB08885AfliberceptBiotechPGF, VEGFA, VEGFB3
DB09301Chondroitin sulfateSmall MoleculeBDNF, CCL2, GDNF, VEGFA4