Abstract
Vascular endothelial growth factor A (VEGF-A or VEGF) is a highly conserved secreted signalling protein best known for its roles in vascular development and angiogenesis. Many non-endothelial roles for VEGF are now established, with the discovery that VEGF and its receptors VEGFR1 and VEGFR2 are expressed in many non-vascular cell-types, as well as various cancers. In addition to secreted VEGF binding to its receptors in the extracellular space at the cell membrane (i.e., in a paracrine or autocrine mode), intracellularly localised VEGF is emerging as an important signalling molecule regulating cell growth, survival, and metabolism. This intracellular mode of signalling has been termed “intracrine”, and refers to the direct action of a signalling molecule within the cell without being secreted. In this review, we describe examples of intracrine VEGF signalling in regulating cell growth, differentiation and survival, both in normal cell homeostasis and development, as well as in cancer. We further discuss emerging evidence for the molecular mechanisms underpinning VEGF intracrine function, as well as the implications this intracellular mode of VEGF signalling may have for use and design of anti-VEGF cancer therapeutics.
Highlights
VEGF Protein FamilyVascular endothelial growth factor A (VEGF-A) is a highly conserved secreted signalling protein and founding member of the VEGF protein family, which includes VEGF-B, VEGF-C, VEGF-D, VEGF-E, and PlGF (Placental Growth Factor) [1]
Whether the MET-induced phosphorylation of VEGFR2 by intracrine VEGF is required for ubiquitination remains to be investigated, but provides an intriguing hypothesis for how intracrine VEGF may function mechanistically
Intracrine VEGF signalling is emerging as an important intracellular pathway regulating cell growth and survival
Summary
Vascular endothelial growth factor A (VEGF-A) is a highly conserved secreted signalling protein and founding member of the VEGF protein family, which includes VEGF-B, VEGF-C, VEGF-D, VEGF-E, and PlGF (Placental Growth Factor) [1]. VEGF-A is best known for its roles in vascular development. While a clear biological role for VEGF-B is yet to be defined, VEGF-C and VEGF-D are strongly implicated in lymphangiogenesis. VEGF-E is encoded by the Orf parapoxvirus and plays important roles in virus infection and associated pathology. PlGF plays roles in angiogenesis and can form functional heterodimers with VEGF-A [1]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
