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IL-17A Promotes the Migration and Invasiveness of Colorectal Cancer Cells Through NF-kB-Mediated MMP Exp
* Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
† Department of General Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Oncology Research 2015, 23(5), 249-256. https://doi.org/10.3727/096504016X14562725373716
Abstract
Interleukin-17A (IL-17A) plays a significant role in many inflammatory diseases and cancers. The aim of this study is to investigate the effect of IL-17A on the invasiveness of colorectal cancer. In the study, we found that IL-17A could promote the migration and invasion of colorectal cancer cells. Furthermore, after being treated with IL-17A, the expression and activity of matrix metalloproteinase 2 (MMP-2) and MMP-9 were upregulated. Moreover, the nuclear/overall fractions and DNA-binding activity of p65 and p50 were dramatically elevated by IL-17A. Pretreatment with a nuclear factor-kB (NF-kB) inhibitor (PDTC) or PI3K/AKT inhibitor (LY294002) was proven to abolish the promoting effect of IL-17A on the invasion ability of colorectal cancer cells and upregulation of MMP-2/9. In conclusion, our findings demonstrated that IL-17A could promote the invasion of colorectal cancer cells by activating the PI3K/AKT/NF-kB signaling pathway and subsequently upregulating the expression of MMP-2/9. Our results suggest that IL-17A could serve as a promising therapeutic target for colorectal cancer.Keywords
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