TRAF4 Regulates Migration, Invasion, and Epithelial‐Mesenchymal Transition via PI3K/AKT Signaling in Hepatocellular Carcinoma
Overexpression of the tumor necrosis factor receptor-associated factor 4 (TRAF4) has been detected in many cancer types and is considered to foster tumor progression. However, the role of TRAF4 in hepatocellular carcinoma (HCC) remains elusive. In this study, we found that TRAF4 was
highly expressed in HCC cell lines and HCC tissues compared with normal liver cell lines and adjacent noncancerous tissues. TRAF4 overexpression in HCC tissues was correlated with tumor quantity and vascular invasion. In vitro studies showed that TRAF4 was associated with HCC cell migration
and invasion. An in vivo study verified that TRAF4 overexpression facilitated metastasis in nude mice. In addition, overexpressed TRAF4 promoted the phosphorylation of Akt and induced Slug overexpression, leading to downregulated E-cadherin and upregulated vimentin, while silencing TRAF4 moderated
the phosphorylation of Akt and repressed the expression of Slug, which resulted in upregulated E-cadherin and downregulated vimentin. These effects were inversed after pretreatment of the PI3K/Akt inhibitor LY294002 or overexpression of constitutively active Akt1. Our study demonstrated that
TRAF4 was involved in promoting HCC cell migration and invasion. The process was induced by the EMT through activation of the PI3K/Akt signaling pathway.
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Epithelial‐mesenchymal transition (EMT);
Hepatocellular carcinoma (HCC);
PI3K/Akt signaling pathway;
Tumor necrosis factor receptor-associated factor 4 (TRAF4)
Document Type: Research Article
Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, P.R. China
Physical Examination Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, P.R. China
Department of Hepatobiliary Surgery, The Six Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, P.R. China
Publication date: 21 September 2017
This article was made available online on 02 March 2017 as a Fast Track article with title: "TRAF4 regulates migration, invasion and the epithelial-mesenchymal transition via PI3K/AKT signaling in hepatocellular carcinoma".
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