Figure 1.

Role of VEGF signaling in OSCC. VEGF is constitutively expressed in oral squamous cell carcinoma. Its secretion can be the result of the activation of different signaling pathways, which includes: (1) the production of hypoxia inducible and HIF-2α by low oxygen levels, (2) the activation of Stat3 by CCL4 (which is constitutively expressed in OSCC) and (3) the activation of COX2 by different inflammatory molecules (commonly overexpressed in OSCC) which activate the NF-kB pathway. The activation of these pathways leads to the transcription of all four variants of VEGF (A–D), which through the activation of VEGF-R1, VEGF-R2 and VEGF-3 on blood and lymphatic endothelial cells, induces angio- and lymphogenesis. Created with BioRender.com.