Figure 3.

Signal transduction pathways activated by VEGF binding to neuropilins.

Notes: Among the growth factors that neuropilins can bind, VEGF is the most described. VEGF has autocrine and paracrine functions and influences tumor cells as well as cells from the tumor microenvironment. VEGF/NRP signaling increases adhesion, migration/invasion, proliferation, and survival, and inhibits differentiation of cells during angiogenesis, lymphangiogenesis, tumor growth, and metastasis. While neuropilins can bind VEGF-A, -B, and -C, most mechanisms that have been described involve VEGF-A and -C. The receptor complexes are either NRP-VEGFR-2 or NRP-cMET for VEGF-A. For VEGF-C, the receptor complex contains NRP and VEGFR-3. Green arrows: activation; red bars: inhibition.

Abbreviations: EMT, epithelial to mesenchymal transition; ERK, extracellular signal-related kinase; FAK, focal adhesion kinase; HGF, hepacyte growth factor; INT, intracellular environment; mTORC1, mammalian target of rapamycin complex 1; NRP, neuropilin; PI3K, phosphoinositide 3 kinase; STAT, signal transducer and activator of transcription; VEGF, vascular endothelial growth factor.