VEGFA (VEGF)
VEGF-A (vascular endothelial growth factor A) is a secreted signal that induces blood vessel growth. Hypoxic tissues release it to recruit a blood supply; tumors release it for the same reason.
Function
VEGF-A is secreted by cells experiencing hypoxia - HIF-1α, which accumulates when oxygen is scarce, directly induces its transcription. It binds VEGFR2 on endothelial cells, driving their proliferation, migration, and survival, and increasing vessel permeability so that plasma proteins leak out and form a scaffold for new vessel growth. Physiologically this is wound healing, the menstrual cycle, and embryonic vascular development; pathologically it is the angiogenic switch by which an avascular tumor acquires a blood supply.
In cancer
Tumors beyond a millimeter or two in diameter need induced vasculature, and VEGF-A is the dominant inducer. The tumor vasculature that VEGF produces is structurally abnormal - leaky, disorganized, poorly perfused - which both feeds the tumor and limits drug delivery. Anti-VEGF therapy (bevacizumab, the antibody; sorafenib and related receptor kinase inhibitors) is approved across several cancers, with the clinical lesson that blockade delays progression and extends survival modestly rather than eradicating disease, and with resistance arriving through alternative angiogenic factors. VEGF-A also participates in the senescence-associated secretory phenotype.
Notes
- Human gene symbol: VEGFA; UniProt P15692; 232 amino acids (precursor); PDGF/VEGF growth factor family; multiple splice isoforms.