Knockdown of CXCR4 Inhibits CXCL12-Induced Angiogenesis in HUVECs through Downregulation of the MAPK/ERK and PI3K/AKT and the Wnt/β-Catenin Pathways.

CXCL12 is an extracellular chemokine binding to cell surface receptor CXCR4. We found that activation of CXCL12/CXCR4 axis stimulated angiogenesis in endothelial cells. Knockdown of CXCR4 in endothelial cells prevented the branch points of angiogenesis. Endothelial cells exposed to CXCL12 presented high level of epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and matrix metalloproteinase MMP-2, but not in CXCR4 knockdown cells. Further studies revealed that activation of CXCL12/CXCR4 axis in vascular endothelial cells stimulates the angiogenesis through upregulation of the MAPK/ERK and PI3K/AKT and Wnt/β-catenin pathways. Conclusion, downregulation of CXCR4 could inhibit angiogenesis in cancer tissues.