Open AccessIL-17A Promotes the Migration and Invasiveness of Colorectal Cancer Cells Through NF-κB-Mediated MMP Expression
Author(s) -
Hongtao Ren,
Zhongwei Wang,
Shuqun Zhang,
Hongbing Ma,
Yali Wang,
Lijun Jia,
Yiming Li
Publication year - 2016
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504016x14562725373716
Subject(s) - downregulation and upregulation , colorectal cancer , pi3k/akt/mtor pathway , cancer research , ly294002 , matrix metalloproteinase , nf κb , protein kinase b , cancer , medicine , interleukin , biology , signal transduction , inflammation , immunology , cytokine , microbiology and biotechnology , gene , biochemistry
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-κB (NF-κB) 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-κB 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.