Angiogenesis Pathway

Preferred Label : Angiogenesis Pathway;

NCIt related terms : VEGF, Hypoxia, and Angiogenesis;

Alternative definition : BIOCARTA: Vascular endothelial growth factor (VEGF) plays a key role in physiological blood vessel formation and pathological angiogenesis such as tumor growth and ischemic diseases. Hypoxia is a potent inducer of VEGF in vitro. The increase in secreted biologically active VEGF protein from cells exposed to hypoxia is partly because of an increased transcription rate, mediated by binding of hypoxia-inducible factor-1 (HIF1) to a hypoxia responsive element in the 5'-flanking region of the VEGF gene. bHLH-PAS transcription factor that interacts with the Ah receptor nuclear translocator (Arnt), and its predicted amino acid sequence, exhibits significant similarity to the hypoxia-inducible factor 1alpha (HIF1a) product. HLF mRNA expression is closely correlated with that of VEGF mRNA. The high expression level of HLF mRNA in the O2 delivery system of developing embryos and adult organs suggests that in a normoxic state, HLF regulates gene expression of VEGF, various glycolytic enzymes, and others driven by the HRE sequence, and may be involved in development of blood vessels and the tubular system of lung. VEGF expression is dramatically induced by hypoxia due in large part to an increase in the stability of its mRNA. HuR binds with high affinity and specificity to the VRS element that regulates VEGF mRNA stability by hypoxia. In addition, an internal ribosome entry site (IRES) ensures efficient translation of VEGF mRNA even under hypoxia. The VHL tumor suppressor (von Hippel-Lindau) regulates also VEGF expression at a post-transcriptional level. The secreted VEGF is a major angiogenic factor that regulates multiple endothelial cell functions, including mitogenesis. Cellular and circulating levels of VEGF are elevated in hematologic malignancies and are adversely associated with prognosis. Angiogenesis is a very complex, tightly regulated, multistep process, the targeting of which may well prove useful in the creation of novel therapeutic agents. Current approaches being investigated include the inhibition of angiogenesis stimulants (e.g., VEGF), or their receptors, blockade of endothelial cell activation, inhibition of matrix metalloproteinases, and inhibition of tumor vasculature. Preclinical, phase I, and phase II studies of both monoclonal antibodies to VEGF and blockers of the VEGF receptor tyrosine kinase pathway indicate that these agents are safe and offer potential clinical utility in patients with hematologic malignancies. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_vegfPathway;

Details

Origin ID

C39264;

UMLS CUI

C1510883;

Semantic type(s)
- Cell Function [UMLS semantic type]
has_gene_product_element
- 1-Phosphatidylinositol 4,5-Bisphosphate Phosphodiesterase Gamma-1 [NCIt concept]
- 3-Phosphoinositide-Dependent Protein Kinase 1 [NCIt concept]
- Aryl Hydrocarbon Receptor Nuclear Translocator [NCIt concept]
- B2 Bradykinin Receptor [NCIt concept]
- Eukaryotic Translation Initiation Factor 1 [NCIt concept]
- Eukaryotic Translation Initiation Factor 1A, X-Chromosomal [NCIt concept]
- Focal Adhesion Kinase 1 [NCIt concept]
- GTPase HRas [NCIt concept]
- Heat Shock Protein HSP 90-Alpha [NCIt concept]
- Hypoxia-Inducible Factor 1-Alpha [NCIt concept]
- Nitric Oxide Synthase, Endothelial [NCIt concept]
- Paxillin [NCIt concept]
- Phosphatidylinositol 3-Kinase Regulatory Subunit Alpha [NCIt concept]
- Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha Isoform [NCIt concept]
- Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma Isoform [NCIt concept]
- Protein Kinase C Alpha Type [NCIt concept]
- RAC-Alpha Serine/Threonine Kinase [NCIt concept]
- SHC-Transforming Protein 1 [NCIt concept]
- Son of Sevenless Homolog 1 [NCIt concept]
- Translation Initiation Factor EIF-2B Subunit Epsilon [NCIt concept]
- Vascular Endothelial Growth Factor A [NCIt concept]
- Vascular Endothelial Growth Factor A 165 Isoform [NCIt concept]
- Vascular Endothelial Growth Factor Receptor 1 [NCIt concept]
- Vascular Endothelial Growth Factor Receptor 2 [NCIt concept]
- Vascular Endothelial Growth Factor Receptor 3 [NCIt concept]
- Von Hippel-Lindau Disease Tumor Suppressor [NCIt concept]
pathway_has_gene_element
- AKT1 wt Allele [NCIt concept]
- ARNT wt Allele [NCIt concept]
- BDKRB2 wt Allele [NCIt concept]
- EIF1 wt Allele [NCIt concept]
- EIF1AX wt Allele [NCIt concept]
- EIF2B5 wt Allele [NCIt concept]
- FLT1 wt Allele [NCIt concept]
- FLT4 wt Allele [NCIt concept]
- HIF1A wt Allele [NCIt concept]
- HRAS wt Allele [NCIt concept]
- HSP90AA1 wt Allele [NCIt concept]
- KDR wt Allele [NCIt concept]
- NOS3 wt Allele [NCIt concept]
- PDPK1 wt Allele [NCIt concept]
- PIK3CA wt Allele [NCIt concept]
- PIK3CG wt Allele [NCIt concept]
- PIK3R1 wt Allele [NCIt concept]
- PLCG1 wt Allele [NCIt concept]
- PRKCA wt Allele [NCIt concept]
- PTK2 wt Allele [NCIt concept]
- PXN wt Allele [NCIt concept]
- SHC1 wt Allele [NCIt concept]
- SOS1 wt Allele [NCIt concept]
- VEGFA wt Allele [NCIt concept]
- VHL wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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