Fig. 8.

A schematic model. PDGF in the tumor microenvironment activates PDGF receptor in ECs, which in turn induces NF-κB-dependent Snail expression, thereby inducing endothelial-mesenchymal transformation (Endo-MT). Snail binds to VEGFR-2 promoter and suppresses VEGFR-2 transcription, resulting in VEGFR-2 down-expression and Endo-MT, and eventually leading to anti-VEGF resistance in ECs. In addition, Endo-MT stimulates PDGF expression in ECs, potentially serving as an autocrine-mediated positive forward feedback loop that drives Endo-MT and EC resistance to anti-VEGF treatment