General Information of the Molecule (ID: Mol00192)
Name
Vascular endothelial growth factor A (VEGFA) ,Homo sapiens
Synonyms
VEGF-A; Vascular permeability factor; VPF; VEGF
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Molecule Type
Protein
Gene Name
VEGFA
Gene ID
7422
Location
chr6:43770184-43786487[+]
Sequence
MNFLLSWVHWSLALLLYLHHAKWSQAAPMAEGGGQNHHEVVKFMDVYQRSYCHPIETLVD
IFQEYPDEIEYIFKPSCVPLMRCGGCCNDEGLECVPTEESNITMQIMRIKPHQGQHIGEM
SFLQHNKCECRPKKDRARQEKKSVRGKGKGQKRKRKKSRYKSWSVYVGARCCLMPWSLPG
PHPCGPCSERRKHLFVQDPQTCKCSCKNTDSRCKARQLELNERTCRCDKPRR
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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. Also binds the DEAR/FBXW7-AS1 receptor.
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Uniprot ID
VEGFA_HUMAN
Ensembl ID
ENSG00000112715
HGNC ID
HGNC:12680
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Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Type(s) of Resistant Mechanism of This Molecule
  RTDM: Regulation by the Disease Microenvironment
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
7 drug(s) in total
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Cisplatin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Gastric cancer [1]
Resistant Disease Gastric cancer [ICD-11: 2B72.1]
Resistant Drug Cisplatin
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K/AKT/MRP0 signaling pathway Activation hsa04151
In Vitro Model BGC-823 cells Gastric Homo sapiens (Human) CVCL_3360
SGC7901 cells Gastric Homo sapiens (Human) CVCL_0520
SGC-7901/DDP cells Gastric Homo sapiens (Human) CVCL_0520
BGC-823/DDP cells Gastric Homo sapiens (Human) CVCL_3360
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
CCK8 assay; Colony formation assay; Flow cytometric cell cycle assay; Annexin V-FITC Apoptosis assay
Mechanism Description HOTAIR was shown to directly bind to and inhibit miR126 expression and then to promote VEGFA and PIk3R2 expression and activate the PI3k/AkT/MRP1 pathway.
Cyclophosphamide
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Breast cancer [2]
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
Sensitive Drug Cyclophosphamide
Molecule Alteration Expression
Down-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
PI3K/AKT signaling pathway Regulation hsa04151
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Drug resistance clonogenic assay
Mechanism Description miR-205 enhances chemosensitivity of breast cancer cells to TAC chemotherapy by suppressing both VEGFA and FGF2, leading to evasion of apoptosis.
Dabrafenib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Disease Class: Melanoma [3]
Resistant Disease Melanoma [ICD-11: 2C30.0]
Resistant Drug Dabrafenib
Molecule Alteration Expression
Up-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
Cell proliferation Activation hsa05200
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
Sk-Mel28 cells Skin Homo sapiens (Human) CVCL_0526
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description miR-126-3p down-regulation contributes to dabrafenib acquired resistance in melanoma by up-regulating ADAM9 and VEGF-A.
Docetaxel
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Breast cancer [2]
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
Sensitive Drug Docetaxel
Molecule Alteration Expression
Down-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
PI3K/AKT signaling pathway Regulation hsa04151
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Drug resistance clonogenic assay
Mechanism Description miR-205 enhances chemosensitivity of breast cancer cells to TAC chemotherapy by suppressing both VEGFA and FGF2, leading to evasion of apoptosis.
Doxorubicin
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Breast cancer [2]
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
Sensitive Drug Doxorubicin
Molecule Alteration Expression
Down-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
PI3K/AKT signaling pathway Regulation hsa04151
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Drug resistance clonogenic assay
Mechanism Description miR-205 enhances chemosensitivity of breast cancer cells to TAC chemotherapy by suppressing both VEGFA and FGF2, leading to evasion of apoptosis.
Disease Class: Non-small cell lung cancer [4]
Sensitive Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
Sensitive Drug Doxorubicin
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description VEGF activates the downstream PI3k/Akt signaling pathway, which is a critical regulator of cellular growth, differentiation, and metabolism. miR-126 could overcome the resistance of NSCLC cells to antineoplastic drugs through inhibition of a VEGF-PI3k/Akt signaling pathway that resulted in the down-regulation of MRP1.
Vincristine
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Non-small cell lung cancer [4]
Sensitive Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
Sensitive Drug Vincristine
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description VEGF activates the downstream PI3k/Akt signaling pathway, which is a critical regulator of cellular growth, differentiation, and metabolism. miR-126 could overcome the resistance of NSCLC cells to antineoplastic drugs through inhibition of a VEGF-PI3k/Akt signaling pathway that resulted in the down-regulation of MRP1.
YN-968D1
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Anaplastic thyroid cancer [5]
Resistant Disease Anaplastic thyroid cancer [ICD-11: 2D10.2]
Resistant Drug YN-968D1
Molecule Alteration Expression
Up-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation VEGFA/VEGFR1 signaling pathway Activation hsa05205
In Vitro Model SkOV3 cells Ovary Homo sapiens (Human) CVCL_0532
H1975 cells Lung Homo sapiens (Human) CVCL_1511
A2780 cells Ovary Homo sapiens (Human) CVCL_0134
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HUT78 cells Lymph Homo sapiens (Human) CVCL_0337
SH-1-V2 cells Esophagus Homo sapiens (Human) N.A.
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
CCK-8 assay
Mechanism Description On VEGFR2 blockage by specific targeting agent, such as Apatinib, FOXK2 could rapidly trigger therapeutic resistance. Mechanical analyses revealed that VEGFA transcriptionally induced by FOXK2 could bind to VEGFR1 as a compensation for VEGFR2 blockage, which promoted angiogenesis by activating ERK, PI3K/AKT and P38/MAPK signaling in human umbilical vein endothelial cells (HUVECs). Synergic effect on anti-angiogenesis could be observed when VEGFR1 suppressor AF321 was included in VEGFR2 inhibition system, which clarified the pivot role of FOXK2 in VEGFR2 targeting therapy resistance.
Disease- and Tissue-specific Abundances of This Molecule
ICD Disease Classification 02
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Gastric cancer [ICD-11: 2B72]
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Differential expression of molecule in resistant diseases
The Studied Tissue Gastric tissue
The Specified Disease Gastric cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 1.64E-01; Fold-change: -5.48E-01; Z-score: -1.45E+00
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 2.69E-01; Fold-change: 4.19E-02; Z-score: 1.14E-01
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Lung cancer [ICD-11: 2C25]
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Differential expression of molecule in resistant diseases
The Studied Tissue Lung
The Specified Disease Lung cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 5.49E-01; Fold-change: 3.76E-02; Z-score: 6.25E-02
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 1.13E-02; Fold-change: -2.51E-01; Z-score: -3.08E-01
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Melanoma [ICD-11: 2C30]
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Differential expression of molecule in resistant diseases
The Studied Tissue Skin
The Specified Disease Melanoma
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 3.08E-01; Fold-change: 1.11E-01; Z-score: 1.82E-01
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Breast cancer [ICD-11: 2C60]
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Differential expression of molecule in resistant diseases
The Studied Tissue Breast tissue
The Specified Disease Breast cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 6.44E-56; Fold-change: 6.58E-01; Z-score: 1.01E+00
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 1.24E-11; Fold-change: 5.13E-01; Z-score: 9.34E-01
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Thyroid cancer [ICD-11: 2D10]
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Differential expression of molecule in resistant diseases
The Studied Tissue Thyroid
The Specified Disease Thyroid cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 4.90E-05; Fold-change: -3.82E-01; Z-score: -4.87E-01
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 4.50E-12; Fold-change: -9.01E-01; Z-score: -1.33E+00
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Tissue-specific Molecule Abundances in Healthy Individuals
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References
Ref 1 LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR-126 to activate the PI3K/AKT/MRP1 genes. Tumour Biol. 2016 Nov 30. doi: 10.1007/s13277-016-5448-5. Online ahead of print.
Ref 2 miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer. Cell Death Dis. 2016 Jun 30;7(6):e2291. doi: 10.1038/cddis.2016.194.
Ref 3 miR-126-3p down-regulation contributes to dabrafenib acquired resistance in melanoma by up-regulating ADAM9 and VEGF-A. J Exp Clin Cancer Res. 2019 Jun 21;38(1):272. doi: 10.1186/s13046-019-1238-4.
Ref 4 miR-126 enhances the sensitivity of non-small cell lung cancer cells to anticancer agents by targeting vascular endothelial growth factor A. Acta Biochim Biophys Sin (Shanghai). 2012 Jun;44(6):519-26. doi: 10.1093/abbs/gms026. Epub 2012 Apr 16.
Ref 5 FOXK2 transcriptionally activating VEGFA induces apatinib resistance in anaplastic thyroid cancer through VEGFA/VEGFR1 pathway .Oncogene. 2021 Oct;40(42):6115-6129. doi: 10.1038/s41388-021-01830-5. Epub 2021 Sep 6. 10.1038/s41388-021-01830-5

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