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
  • View Affiliations

  • 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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Copy and paste a formatted citation
APA
Zhang, Y.H., Yan, H.Q., Wang, F., Wang, Y.Y., Jiang, Y.N., Wang, Y.N., & Gao, F.G. (2015). TIPE2 inhibits TNF-α-induced hepatocellular carcinoma cell metastasis via Erk1/2 downregulation and NF-κB activation. International Journal of Oncology, 46, 254-264. https://doi.org/10.3892/ijo.2014.2725
MLA
Zhang, Y. H., Yan, H. Q., Wang, F., Wang, Y. Y., Jiang, Y. N., Wang, Y. N., Gao, F. G."TIPE2 inhibits TNF-α-induced hepatocellular carcinoma cell metastasis via Erk1/2 downregulation and NF-κB activation". International Journal of Oncology 46.1 (2015): 254-264.
Chicago
Zhang, Y. H., Yan, H. Q., Wang, F., Wang, Y. Y., Jiang, Y. N., Wang, Y. N., Gao, F. G."TIPE2 inhibits TNF-α-induced hepatocellular carcinoma cell metastasis via Erk1/2 downregulation and NF-κB activation". International Journal of Oncology 46, no. 1 (2015): 254-264. https://doi.org/10.3892/ijo.2014.2725