J Cancer 2020; 11(15):4406-4412. doi:10.7150/jca.40656

Research Paper

Interleukin 17A promotes gallbladder cancer invasiveness via ERK/NF-κB signal pathway mediated epithelial-to-mesenchymal transition

Kunlun Chen1, Hongwei Tang1, Pengfei Zhu1, Jianwen Ye1, Dong Liu2, Yansong Pu3, Lei Zhang4✉, Wenlong Zhai1✉

1. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China
2. Departments of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, China
3. Departments of General Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, China
4. Hepatic Surgery Center, Institute of Hepato-Pancreato-Bililary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
Kunlun Chen and Hongwei Tang contributed equally.

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Citation:
Chen K, Tang H, Zhu P, Ye J, Liu D, Pu Y, Zhang L, Zhai W. Interleukin 17A promotes gallbladder cancer invasiveness via ERK/NF-κB signal pathway mediated epithelial-to-mesenchymal transition. J Cancer 2020; 11(15):4406-4412. doi:10.7150/jca.40656. Available from http://www.jcancer.org/v11p4406.htm

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Abstract

As a pro-inflammatory cytokine, Interleukin 17A (IL-17A) plays an important role in pathology of tumor microenvironment and inflammatory diseases. In this study, we intend to investigate the role of IL-17A on the metastasis of gallbladder cancer (GBC) and related mechanisms. The serum levels of IL-17A were associated with node metastasis and advanced stage. We also found the pro-invasion effect of IL-17A on GBC cells. When treated with IL-17A, the protein level of epithelial marker E-cadherin in GBC cells was significantly down-regulated, while the protein level of the mesenchymal phenotype marker vimentin was significantly increased. IL-17A increased the expression of transcription factor slug, the phosphorylation of ERK1/2 and the nuclear translocation of NF-κB/p50 and p65 in a concentration-dependent manner. Pretreatment of cells with U0126 could reverse the nuclear translocation of NF-κB/p50 and p65 and EMT induced by IL-17A. IL-17A promotes gallbladder cancer invasiveness via ERK/NF-κB signal pathway mediated epithelial-to-mesenchymal transition. As a new therapeutic targets and diagnostic marker, IL-17A may play an important role in the treatment of GBC.

Keywords: Interleukin 17A, gallbladder cancer, epithelial-mesenchymal transition, invasiveness, ERK/ nuclear factor-κB signal pathway