Fig. 3

Effects of FGFR signaling on the vascular system. On the one hand, TGF-β facilitates the heterodimeric conversion of FGFR to promote EMT. On the other hand, FGF/FGFR signaling blocks TGF-β activation via let-7 miRNA and Smad2 activation via RAS/MAPK signaling, thus preventing EMT in endothelial cells. FGF promotes endothelial cell adhesion and tight junctions through the coupling of p120-cadherin and VE-cadherin and stimulates matrix metalloproteinase 2 (MMP2) and MMP9 shedding from the cell surface, leading to ECM degradation and promoting angiogenesis. FGF/FGFR also controls the expression of the glycolytic enzyme hexokinase 2 (HK2) via c-MYC, which assists in the metabolism, proliferation and migration of vascular endothelial cells. FGF is involved in the inhibition of expression and secretion of endothelial VCAM1, E-selectin, and ICAM1, which in turn impairs T-cell homing and recruitment. TGF-β, transforming growth factor beta; EMT, epithelial-mesenchymal transition; VCAM1, vascular cell adhesion molecule 1; ICAM1, intercellular cell adhesion molecule 1; ECM, extracellular matrix