Expression of vascular endothelial growth factor receptors and invasion and metastasis of hepatocellular carcinoma / 临床肝胆病杂志

ABSTRACT

Vascular endothelial growth factor receptors (VEGFRs) consist of three receptor tyrosine kinase (RTK) superfamily members and two non-RTK superfamily members and bind to the ligand in a non-one-to-one way. VEGFRs mediate various signaling pathways such as Raf1→MAP2K1/2→ERK1/2 through cell surface receptor internalization and thus promote the proliferation of hepatocellular carcinoma cells, angiogenesis, and lymphangiogenesis. VEGFRs can be highly expressed in local cancerous lesions of liver cancer patients, which is a key factor mediating malignant proliferation, invasion, and metastasis of hepatocellular carcinoma, and the expression of VEGFRs is negatively correlated with progression-free survival. Matrix metalloproteinase-9 and heat shock protein 90β can upregulate VEGFRs to promote the proliferation and metastasis of hepatoma cells, while miR-203a, miR-378a, and miR-199a-3p can downregulate VEGFR expression and inhibit hepatoma cell infiltration. Targeted drug therapy based on VEGFR can induce the apoptosis of hepatoma cells, block tumor angiogenesis, and delay disease progression.