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

Kunlun Chen; Hongwei Tang; Pengfei Zhu; Jianwen Ye; Dong Liu; Yansong Pu; Lei Zhang; Wenlong Zhai

doi:10.7150/jca.40656

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

J Cancer. 2020 May 18;11(15):4406-4412. doi: 10.7150/jca.40656. eCollection 2020.

Authors

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

Affiliations

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.

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