國家衛生研究院 NHRI:Item 3990099045/7126
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    题名: 14-3-3epsilon overexpression contributes to epithelial-mesenchymal transition of hepatocellular carcinoma
    其它题名: 14-3-3ε overexpression contributes to epithelial-mesenchymal transition of hepatocellular carcinoma
    作者: Liu, TA;Jan, YJ;Ko, BS;Liang, SM;Chen, SC;Wang, J;Hsu, C;Wu, YM;Liou, JY
    贡献者: Institute of Cellular and Systems Medicine
    摘要: BACKGROUND: 14-3-3epsilon is implicated in regulating tumor progression, including hepatocellular carcinoma (HCC). Our earlier study indicated that elevated 14-3-3epsilon expression is significantly associated with higher risk of metastasis and lower survival rates of HCC patients. However, the molecular mechanisms of how 14-3-3epsilon regulates HCC tumor metastasis are still unclear. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, we show that increased 14-3-3epsilon expression induces HCC cell migration and promotes epithelial-mesenchymal transition (EMT), which is determined by the reduction of E-cadherin expression and induction of N-cadherin and vimentin expression. Knockdown with specific siRNA abolished 14-3-3epsilon-induced cell migration and EMT. Furthermore, 14-3-3epsilon selectively induced Zeb-1 and Snail expression, and 14-3-3epsilon-induced cell migration was abrogated by Zeb-1 or Snail siRNA. In addition, the effect of 14-3-3epsilon-reduced E-cadherin was specifically restored by Zeb-1 siRNA. Positive 14-3-3epsilon expression was significantly correlated with negative E-cadherin expression, as determined by immunohistochemistry analysis in HCC tumors. Analysis of 14-3-3epsilon/E-cadherin expression associated with clinicopathological characteristics revealed that the combination of positive 14-3-3epsilon and negative E-cadherin expression is significantly correlated with higher incidence of HCC metastasis and poor 5-year overall survival. In contrast, patients with positive 14-3-3epsilon and positive E-cadherin expression had better prognostic outcomes than did those with negative E-cadherin expression. SIGNIFICANCE: Our findings show for the first time that E-cadherin is one of the downstream targets of 14-3-3epsilon in modulating HCC tumor progression. Thus, 14-3-3epsilon may act as an important regulator in modulating tumor metastasis by promoting EMT as well as cell migration, and it may serve as a novel prognostic biomarker or therapeutic target for HCC.
    日期: 2013-03
    關聯: PLoS ONE. 2013 Mar;8(3):Article number e57968.
    Link to: http://dx.doi.org/10.1371/journal.pone.0057968
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1932-6203&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000316936100061
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84874599208
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