A20 inhibits the motility of HCC cells induced by TNF-α

• DOI: 10.18632/oncotarget.7521
• Publication Date: 2016-02-20T07:53:17Z
• Authors: Xianteng Wang; Chao Ma; Zhaoyun Zong; Ying Xiao; Na Li; Chun Guo; Lining Zhang; Yongyu Shi
• Keywords: Male; rac1 GTP-Binding Protein; 0301 basic medicine; Mice, Inbred BALB C; Carcinoma, Hepatocellular; Epithelial-Mesenchymal Transition; Tumor Necrosis Factor-alpha; Liver Neoplasms; Mice, Nude; Apoptosis; Xenograft Model Antitumor Assays; Mice; 03 medical and health sciences; Cell Movement; Focal Adhesion Kinase 1; Biomarkers, Tumor; Tumor Cells, Cultured; Animals; Humans; Tumor Necrosis Factor alpha-Induced Protein 3; Research Paper; Cell Proliferation; Signal Transduction

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.