Dataset Information

14-3-3? overexpression contributes to epithelial-mesenchymal transition of hepatocellular carcinoma.

ABSTRACT:

Background

14-3-3? is implicated in regulating tumor progression, including hepatocellular carcinoma (HCC). Our earlier study indicated that elevated 14-3-3? expression is significantly associated with higher risk of metastasis and lower survival rates of HCC patients. However, the molecular mechanisms of how 14-3-3? regulates HCC tumor metastasis are still unclear.

Methodology and principal findings

In this study, we show that increased 14-3-3? 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 14-3-3?-induced cell migration and EMT. Furthermore, 14-3-3? selectively induced Zeb-1 and Snail expression, and 14-3-3?-induced cell migration was abrogated by Zeb-1 or Snail siRNA. In addition, the effect of 14-3-3?-reduced E-cadherin was specifically restored by Zeb-1 siRNA. Positive 14-3-3? expression was significantly correlated with negative E-cadherin expression, as determined by immunohistochemistry analysis in HCC tumors. Analysis of 14-3-3?/E-cadherin expression associated with clinicopathological characteristics revealed that the combination of positive 14-3-3? 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 14-3-3? 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 14-3-3? in modulating HCC tumor progression. Thus, 14-3-3? 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.

SUBMITTER: Liu TA

PROVIDER: S-EPMC3590290 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

14-3-3ε overexpression contributes to epithelial-mesenchymal transition of hepatocellular carcinoma.

Liu Tzu-An TA Jan Yee-Jee YJ Ko Bor-Sheng BS Liang Shu-Man SM Chen Shyh-Chang SC Wang John J Hsu Chiun C Wu Yao-Ming YM Liou Jun-Yang JY

PloS one 20130306 3

<h4>Background</h4>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.<h4>Methodology and principal findings</h4>In this study, we show that increased 14-3-3ε expression induces HCC cell migrati ...[more]

PMID: 23483955

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