Liu K, Wu X, Zang X et al.
Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, P.R. China.
Oncology research. Mar 2017.
The tumor necrosis factor receptor-associated factor 4 (TRAF4) overexpression has been detected in many cancer types and 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 line and adjacent noncancerous tissue. TRAF4 overexpression in HCC tissues was correlated with tumor numbers and vascular invasion. in vitro studies showed that TRAF4 was associated with HCC cells migration and invasion. In vivo study verified that TRAF4 overexpression faciliated metastasis in nude mice. In addition, overexpressed TRAF4 promoted the phosphorylation of Akt and induced Slug overexpression, leading to down-regulated E-cadherin and up-regulated Vimentin, while silencing TRAF4 moderated the phosphorylation of Akt and repressed the expression of Slug, which resulted in up-regulated E-cadherin and down-regulated Vimentin. These effects were inversed after pretreatment of 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 PI3K/Akt signaling pathway.