TIPE2 inhibits TNF-α-induced hepatocellular carcinoma cell metastasis via Erk1/2 downregulation and NF-κB activation

Zhang,Yue Hua; Yan,Hong Qiong; Wang,Fang; Wang,Yan Yan; Jiang,Yi Na; Wang,Yi Nan; Gao,Feng Guang

doi:10.3892/ijo.2014.2725

TIPE2 inhibits TNF-α-induced hepatocellular carcinoma cell metastasis via Erk1/2 downregulation and NF-κB activation

Authors:
- Yue Hua Zhang
- Hong Qiong Yan
- Fang Wang
- Yan Yan Wang
- Yi Na Jiang
- Yi Nan Wang
- Feng Guang Gao
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Affiliations: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, P.R. China
Published online on: October 23, 2014 https://doi.org/10.3892/ijo.2014.2725
Pages: 254-264

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Abstract

Tumor necrosis factor-α-induced protein 8-like 2 (TNFAIP8L2, TIPE2), which belongs to the TNF-α-induced protein 8 family, is a negative regulator of immune homeostasis. Although pro-inflammatory cytokines such as TNF-α have been reported to be involved in liver carcinoma metastasis, the effect of TIPE2 on hepatocellular carcinoma metastasis remains unknown. We demonstrate that TNF-α clearly augments MMP-13/MMP-3 expression and promotes cell migration in HepG2 cells through activation of the Erk1/2-NF-κB pathways. Interestingly, in addition to human PBLs, macrophages and fibroblasts, liver cancer cells specifically express TNF-α following LPS treatment. Most importantly, TIPE2 overexpression efficiently abrogates the effects of LPS on TNF-α secretion and abolishes the effects of TNF-α on MMP-13/MMP-3 upregulation, cell migration and Erk1/2-NF-κB activation. Taken together, these findings demonstrate that TIPE2 was able to suppress TNF-α-induced hepatocellular carcinoma metastasis by inhibiting Erk1/2 and NF-κB activation, indicating that both TNF-α and TIPE2 might be potential targets for the treatment of HCC metastasis.

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