The Role of DLL4-Notch-VEGFR2 Signaling Pathway in Tumor Angiogenesis

Abstract

Tumor angiogenesis is the center of tumor growth and metastasis, and it increases the supply of nutrients and oxygen to tumors, thereby supporting tumor growth and progression. Vascular endothelial growth factor (VEGF) is a stimulator of angiogenesis and also plays a key role in the process of angiogenesis. Overexpression of VEGF is associated with tumor angiogenesis, promotion of tumor growth and reduced survival rate of patients. Notch signaling is a key pathway that regulates the response to angiogenesis stimulation during embryonic vascular development and postnatal angiogenesis, and is involved in multiple steps of angiogenesis. Dll4 is the only Notch ligand mainly expressed in endothelial cells, which can propagate by activating Notch signal and regulate tumor angiogenesis. Notch signaling pathway and VEGF pathway have both independent and synergistic effects, and Notch is necessary for VEGF-mediated vascular remodeling. The pathways cross each other and jointly regulate tumor angiogenesis. This review reviews the relationship between dLL4-notch-VEGFR2 signaling pathway composition, transduction and regulation and tumor angiogenesis. Combined blocking of DLL4-notch-VEGFR2 signaling pathway can significantly reduce vascular perfusion, resulting in vascular degeneration and reduced tumor survival. It can destroy the vascular system and survival ability of the primary tumor more than blocking alone, thus providing a new idea for the treatment of tumor, which is of great significance for the future anti-angiogenesis therapy.