Interleukin-8 promotes cell migration through integrin αvβ6 upregulation in colorectal cancer

Colorectal cancer (CRC), which is notorious for high morbidity and mortality around the world, shows a predilection for metastasis to liver. Interleukin-8 (IL-8), a chemokine with a defining CXC amino acid motif, has been reported to promote CRC cell migration and is associated with poor prognosis of CRC. However, the underlying molecular mechanism of IL-8-mediated migration remains obscure. In this study, we first demonstrated the cross talk between IL-8 and integrin alpha v beta 6. We analyzed 139 human CRC samples, and found that the immunohistochemical expression of alpha v beta 6 was significantly correlated with expression of IL-8. Furthermore, IL-8 increased the migration through integrin alpha v beta 6 in human CRC cells, and both CXCR1 and CXCR2 were primarily involved during the process. IL-8 upregulated alpha v beta 6 expression in a dose-dependent manner through activation of ERK and Ets-1 signaling pathway. Taken together, our results indicated that IL-8 enhances the migration of CRC cells by increasing alpha v beta 6 integrin expression through the ERK/Ets-1 pathway. Targeting integrin alpha v beta 6 in IL-8 expressing tumors might be a potential therapeutic strategy for CRC patients. (C) 2014 Elsevier Ireland Ltd. All rights reserved.