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.
ABSTRACT
Vascular endothelial growth factor ( VEGF) is a mitogen that specifically acts on glyco-sylated cells of endothelial cells, enhances vascular permeability, induces angiogenesis, promotes the growth, invasion and metastasis of hepatocellular carcinoma cells. The prognosis of patients with high expres-sion of vascular endothelial growth factor is poor. Down-regulation of VEGF can significantly inhibit the ma-lignant proliferation of hepatocellular carcinoma ( HCC) and improve patients′ prognosis. This article sys-tematically reviewed the recent advances in VEGF expression and its role in promoting the invasion and me-tastasis of hepatocellular carcinoma cells as well as in VEGF-targeted anti-angiogenesis therapy for patients with HCC, aiming to provide some novel ideas to delay the disease progression in the patients.