Chemokine receptor 7 targets the vascular endothelial growth factor via the AKT/ERK pathway to regulate angiogenesis in colon cancer

BACKGROUND: Studies have shown that CXCR7 is expressed in many tumors. The aim of the present study was to investigate the function of CXCR7 in colon cancer. Although evidence indicates that CXCR7 promotes angiogenesis in colon cancer, the mechanism involved in this process remains unclear. METHODS: The expression of CXCR7 in colon cancer was evaluated by quantitative reverse-transcription polymerase chain reaction and western blotting. After transfection, cell proliferation, migration, and lumen formation were measured in vitro. Immunohistochemistry and western blotting were used to identify the functional target of CXCR7 in vivo and in vitro. RESULTS: In this study, CXCR7 was differentially expressed in four colon cancer cell lines. The proliferation and migration experiments showed that overexpression of CXCR7 enhanced cell growth and migration. Moreover, the tube formation assays showed that co-culture of colon cancer cells overexpressing CXCR7 with human umbilical vein endothelial cells significantly promoted tube formation in the latter cells. Conversely, the stable knockdown of CXCR7 significantly reduced this malignant activity. In addition, we found that CXCR7 activates the AKT and ERK pathways in colon cancer cells. The phosphorylation of AKT and ERK, as well as the expression of the vascular endothelial growth factor, can be inhibited using the LY294002 and U0126 inhibitors. Furthermore, the angiogenic ability of CXCR7-induced colon cancer cells was eliminated. CONCLUSION: Expression of CXCR7 contributes to colon cancer growth and angiogenesis, by activating the AKT and ERK pathways. CXCR7 provides a potential therapeutic target against colon cancer.