Hallmarks of Cancer

Most of the gene mutations that causes cancer appear to regulate different pathways, which have been termed the Hallmarks of Cancer. Sustained angiogenesis is one of the hallmark feature of solid tumors


The intricately branched circulatory network of vascular endothelial and supporting cells is essential for transporting oxygen, nutrients, and signaling molecules to and the removal of carbon dioxide and metabolic end products from cells, tissues, and organs. Angiogenesis is the process of new blood vessel formation from pre-existing vascular networks by capillary sprouting. During this process, mature endothelial cells divide and are incorporated into new capillaries. Vascular endothelial growth factor (VEGF) signaling is required for the full execution of angiogenesis.

VEGFA and VEGF receptors

VEGFA is the prototype member of a family of proteins that includes VEGFB, VEGFC, VEGFD, VEGFE (a virally encoded protein) and placental growth factor (PlGF also known as PGF). These proteins, which are structurally related to the platelet-derived growth factor (PDGF) family of proteins have a range of tissue distributions and functions VEGFA gene, isoforms and encoded proteins. Proteolysis plays an important part in regulating the biological activity of VEGFA proteins. The interactions of VEGFA family members with different VEGFRs are outlined in figure.

Of the two RTKs, VEGFR2 is the main mediator of the roles of VEGFA in cell proliferation, angiogenesis and vessel permeabilization. Binding of VEGFA to VEGFR2 on endothelial cells leads to receptor dimerization and autophosphorylation, Regulation of VEGFA gene expression. The expression of VEGFA is primarily stimulated by hypoxia, mediated by the hypoxia-inducible factor (HIF), which also triggers the expression of other hypoxiaregulated genes. VEGFA expression is also regulated by other factors, such as epidermal growth factor (EGF) and PDGF9, and by oncogenic mutations.