Open Access
ARTICLE
TRAF4 Regulates Migration, Invasion, and Epithelial–Mesenchymal Transition via PI3K/AKT Signaling in Hepatocellular Carcinoma
Kairui Liu*, Xiaolin Wu*, Xian Zang†, Zejian Huang*, Zeyu Lin‡, Wenliang Tan*, Xiang Wu*, Wenrou Hu*, Baoqi Li*, Lei Zhang*
* 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
Oncology Research 2017, 25(8), 1329-1340. https://doi.org/10.3727/096504017X14876227286564
Abstract
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.
Keywords
Cite This Article
APA Style
Liu, K., Wu, X., Zang, X., Huang, Z., Lin, Z. et al. (2017). TRAF4 regulates migration, invasion, and epithelial–mesenchymal transition via PI3K/AKT signaling in hepatocellular carcinoma. Oncology Research, 25(8), 1329-1340. https://doi.org/10.3727/096504017X14876227286564
Vancouver Style
Liu K, Wu X, Zang X, Huang Z, Lin Z, Tan W, et al. TRAF4 regulates migration, invasion, and epithelial–mesenchymal transition via PI3K/AKT signaling in hepatocellular carcinoma. Oncol Res. 2017;25(8):1329-1340 https://doi.org/10.3727/096504017X14876227286564
IEEE Style
K. Liu et al., "TRAF4 Regulates Migration, Invasion, and Epithelial–Mesenchymal Transition via PI3K/AKT Signaling in Hepatocellular Carcinoma," Oncol. Res., vol. 25, no. 8, pp. 1329-1340. 2017. https://doi.org/10.3727/096504017X14876227286564