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.