title: A20 inhibits the motility of HCC cells induced by TNF-α.
abstract: Metastasis of hepatocellular carcinoma (HCC) can be facilitated by TNF-α, a prototypical inflammatory cytokine in the HCC microenvironment. A20 is a negative regulator of NF-κB signaling pathway. In the present study we ask whether A20 plays a role in HCC metastasis. We found that A20 expression was downregulated in the invasive cells of microvascular invasions (MVI) compared with the noninvasive cells in 89 tissue samples from patients with HCC by immunochemistry methods. Overexpression of A20 in HCC cell lines inhibited their motility induced by TNF-α. Furthermore, the overexpression of A20 inhibited epithelial-mesenchymal transition (EMT), FAK activation and RAC1 activity. By contrast, knockdown of A20 in one HCC cell line results in the converse. In addition, the overexpression of A20 restrained the formation of MVI in HCC xenograft in nude mice treated with TNF-α. All the results suggested that A20 functioned as a negative regulator in motility of HCC cells induced by TNF-α.
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Xianteng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Zhaoyun
authors.initials: Z
authors.lastname: Zong
authors.affiliation: Laboratory of Cellular and Molecular Medicine, Shandong University School of Medicine, Jinan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Lining
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, China.
authors.forename: Yongyu
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C107953:RAC1 protein, human; D014409:Tumor Necrosis Factor-alpha; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D020830:rac1 GTP-Binding Protein
keywords: A20; TNF-α; TNFAIP3; hepatocellular carcinoma; metastasis