There are four possible mechanisms by which CXCL12/CXCR4 regulates tumor angiogenesis: 1) upregulates vascular endothelial growth factor (VEGF) expression in tumor tissue through the PI3K/Akt signaling pathway; 2) reduces the expression of glycolytic enzyme phosphoglycerate kinase 1 (PGK1) which suppresses the secretion of VEGF; 3) upregulates several angiogenesis-associated genes in cancer cells; and 4) directs the recruitment of endothelial progenitor cells to the vicinity of neovascularization. This evidence concerns the gene CXCL12 and cancer.