Molecule Information
General Information of the Molecule (ID: Mol00192)
Name |
Vascular endothelial growth factor A (VEGFA)
,Homo sapiens
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Synonyms |
VEGF-A; Vascular permeability factor; VPF; VEGF
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Molecule Type |
Protein
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Gene Name |
VEGFA
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Gene ID | |||||
Location |
chr6:43770184-43786487[+]
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Sequence |
MNFLLSWVHWSLALLLYLHHAKWSQAAPMAEGGGQNHHEVVKFMDVYQRSYCHPIETLVD
IFQEYPDEIEYIFKPSCVPLMRCGGCCNDEGLECVPTEESNITMQIMRIKPHQGQHIGEM SFLQHNKCECRPKKDRARQEKKSVRGKGKGQKRKRKKSRYKSWSVYVGARCCLMPWSLPG PHPCGPCSERRKHLFVQDPQTCKCSCKNTDSRCKARQLELNERTCRCDKPRR Click to Show/Hide
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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 | |||||
Ensembl ID | |||||
HGNC ID | |||||
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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
Cisplatin
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Disease Class: Gastric cancer | [1] | |||
Resistant Disease | Gastric cancer [ICD-11: 2B72.1] | |||
Resistant Drug | Cisplatin | |||
Molecule Alteration | Expression | Up-regulation |
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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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Disease Class: Breast cancer | [2] | |||
Sensitive Disease | Breast cancer [ICD-11: 2C60.3] | |||
Sensitive Drug | Cyclophosphamide | |||
Molecule Alteration | Expression | Down-regulation |
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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
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Regulation by the Disease Microenvironment (RTDM) | ||||
Disease Class: Melanoma | [3] | |||
Resistant Disease | Melanoma [ICD-11: 2C30.0] | |||
Resistant Drug | Dabrafenib | |||
Molecule Alteration | Expression | Up-regulation |
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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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Disease Class: Breast cancer | [2] | |||
Sensitive Disease | Breast cancer [ICD-11: 2C60.3] | |||
Sensitive Drug | Docetaxel | |||
Molecule Alteration | Expression | Down-regulation |
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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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Disease Class: Breast cancer | [2] | |||
Sensitive Disease | Breast cancer [ICD-11: 2C60.3] | |||
Sensitive Drug | Doxorubicin | |||
Molecule Alteration | Expression | Down-regulation |
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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 |
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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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
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 |
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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
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Disease Class: Anaplastic thyroid cancer | [5] | |||
Resistant Disease | Anaplastic thyroid cancer [ICD-11: 2D10.2] | |||
Resistant Drug | YN-968D1 | |||
Molecule Alteration | Expression | Up-regulation |
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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
Gastric cancer [ICD-11: 2B72]
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
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Disease-specific Molecule Abundances | Click to View the Clearer Original Diagram | |
Lung cancer [ICD-11: 2C25]
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
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Disease-specific Molecule Abundances | Click to View the Clearer Original Diagram | |
Melanoma [ICD-11: 2C30]
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
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Disease-specific Molecule Abundances | Click to View the Clearer Original Diagram | |
Breast cancer [ICD-11: 2C60]
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
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Disease-specific Molecule Abundances | Click to View the Clearer Original Diagram | |
Thyroid cancer [ICD-11: 2D10]
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
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Disease-specific Molecule Abundances | Click to View the Clearer Original Diagram | |
Tissue-specific Molecule Abundances in Healthy Individuals
References
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