Interleukin-6 Promotes Epithelial-Mesenchymal Transition and Cell Invasion through Integrin <i>β</i>6 Upregulation in Colorectal Cancer
Qi Sun, Yukui Shang, Fengkai Sun, Xiwen Dong, Jun Niu, Fanni Li
Abstract
The metastatic potential of colorectal cancer (CRC) is intensively promoted by the tumor microenvironment (TME) in a paracrine manner. As a pleiotropic inflammatory cytokine, Interleukin-6 (IL-6) is produced and involved in CRC, the same scenario where integrin α v β 6 also becomes upregulated. However, the relationship between IL-6 and integrin α v β 6 as well as their involvement in the crosstalk between CRC and TME remains largely unclear. In the present study, we demonstrated a positive correlation between the expression of IL-6 and integrin β 6 in CRC samples. The mutually promotive interaction between CRC and TME was further determined by an indirect coculture system. CRC cells could augment the secretion of IL-6 from fibroblasts, which in return induced invasion and integrin β 6 expression of CRC cells. Through the classic IL-6 receptor/STAT-3 signaling pathway, IL-6 mediated the upregulation of integrin β 6, which was involved in the invasion and epithelial-mesenchymal transition of CRC cells induced by IL-6. Taken together, our results reveal a paracrine crosstalk between IL-6 signals originating from the TME and increased the integrin β 6 level of CRC. IL-6 induces CRC invasion via upregulation of integrin β 6 through the IL-6 receptor/STAT-3 signaling pathway. Combined inhibition of IL-6 along with integrin β 6-targeted strategy may indicate new directions for antitumor strategies for CRC.