title: TRAF4 Regulates Migration, Invasion, and Epithelial-Mesenchymal Transition via PI3K/AKT Signaling in Hepatocellular Carcinoma.
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.
authors.forename: Kairui
authors.initials: K
authors.lastname: Liu
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wu
authors.forename: Xian
authors.initials: X
authors.lastname: Zang
authors.forename: Zejian
authors.initials: Z
authors.lastname: Huang
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Lin
authors.forename: Wenliang
authors.initials: W
authors.lastname: Tan
authors.forename: Xiang
authors.initials: X
authors.lastname: Wu
authors.forename: Wenrou
authors.initials: W
authors.lastname: Hu
authors.forename: Baoqi
authors.initials: B
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D053449:TNF Receptor-Associated Factor 4 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
chemical_list: D053449:TNF Receptor-Associated Factor 4; C506367:TRAF4 protein, human; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt