title: TIPE2 inhibits TNF-α-induced hepatocellular carcinoma cell metastasis via Erk1/2 downregulation and NF-κB activation.
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.
authors.affiliation: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, P.R. China.
authors.forename: Yue Hua
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, P.R. China.
authors.forename: Hong Qiong
authors.initials: HQ
authors.lastname: Yan
authors.affiliation: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, P.R. China.
authors.forename: Yan Yan
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, P.R. China.
authors.forename: Yi Na
authors.initials: YN
authors.lastname: Jiang
authors.affiliation: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, P.R. China.
authors.forename: Yi Nan
authors.initials: YN
authors.lastname: Wang
authors.affiliation: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, P.R. China.
authors.forename: Feng Guang
authors.initials: FG
authors.lastname: Gao
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009362:Neoplasm Metastasis; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C552057:TNFAIP8L2 protein, human; D014409:Tumor Necrosis Factor-alpha; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3