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

Xianteng Wang; Chao Ma; Zhaoyun Zong; Ying Xiao; Na Li; Chun Guo; Lining Zhang; Yongyu Shi

doi:10.18632/oncotarget.7521

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Research Papers:

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

Xianteng Wang, Chao Ma, Zhaoyun Zong, Ying Xiao, Na Li, Chun Guo, Lining Zhang and Yongyu Shi _

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Oncotarget. 2016; 7:14742-14754. https://doi.org/10.18632/oncotarget.7521

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Abstract

Xianteng Wang1,*, Chao Ma2,*, Zhaoyun Zong1,*, Ying Xiao3, Na Li1, Chun Guo1, Lining Zhang1, Yongyu Shi1

1Department of Immunology, Shandong University School of Medicine, Jinan, China

2Department of Pathology, Qilu Hospital of Shandong University, Jinan, China

3Laboratory of Cellular and Molecular Medicine, Shandong University School of Medicine, Jinan, China

*These authors contributed equally to this work

Correspondence to:

Yongyu Shi, e-mail: [email protected]

Keywords: hepatocellular carcinoma, A20, TNFAIP3, metastasis, TNF-α

Received: June 11, 2015 Accepted: January 26, 2016 Published: February 20, 2016

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.

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Research Papers:

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

Abstract