|Title:||14-3-3ε Overexpression Contributes to Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma||Authors:||Liu T.-A.
|Issue Date:||2013||Journal Volume:||8||Journal Issue:||3||Source:||PLoS ONE||Abstract:||
Background: 14-3-3ε is implicated in regulating tumor progression, including hepatocellular carcinoma (HCC). Our earlier study indicated that elevated 14-3-3ε expression is significantly associated with higher risk of metastasis and lower survival rates of HCC patients. However, the molecular mechanisms of how 14-3-3ε regulates HCC tumor metastasis are still unclear. Methodology and Principal Findings: In this study, we show that increased 14-3-3ε 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 14-3-3ε-induced cell migration and EMT. Furthermore, 14-3-3ε selectively induced Zeb-1 and Snail expression, and 14-3-3ε-induced cell migration was abrogated by Zeb-1 or Snail siRNA. In addition, the effect of 14-3-3ε-reduced E-cadherin was specifically restored by Zeb-1 siRNA. Positive 14-3-3ε expression was significantly correlated with negative E-cadherin expression, as determined by immunohistochemistry analysis in HCC tumors. Analysis of 14-3-3ε/E-cadherin expression associated with clinicopathological characteristics revealed that the combination of positive 14-3-3ε 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 14-3-3ε 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 14-3-3ε in modulating HCC tumor progression. Thus, 14-3-3ε 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. ? 2013 Liu et al.
|ISSN:||1932-6203||DOI:||10.1371/journal.pone.0057968||SDG/Keyword:||nerve cell adhesion molecule; protein 14 3 3; protein 14 3 3 epsilon; small interfering RNA; transcription factor Snail; transcription factor ZEB1; unclassified drug; uvomorulin; vimentin; cadherin; homeodomain protein; protein 14 3 3; snail family transcription factors; transcription factor; YWHAE protein, human; ZEB1 protein, human; article; cancer cell; cancer growth; cancer incidence; cancer patient; cancer prognosis; cancer survival; cell migration; clinical feature; controlled study; correlation analysis; enzyme activity; epithelial mesenchymal transition; human; human cell; human tissue; liver cell carcinoma; major clinical study; metastasis; outcome assessment; protein expression; protein function; cell motion; gene expression regulation; genetics; Kaplan Meier method; liver tumor; metabolism; middle aged; pathology; prognosis; tumor cell line; upregulation; 14-3-3 Proteins; Cadherins; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Movement; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Homeodomain Proteins; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Middle Aged; Neoplasm Metastasis; Prognosis; Transcription Factors; Up-Regulation
|Appears in Collections:||醫學系|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.