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Open Access Research article

14-3-3σ induces heat shock protein 70 expression in hepatocellular carcinoma

Chia-Chia Liu12, Yee-Jee Jan3, Bor-Sheng Ko4, Yao-Ming Wu5, Shu-Man Liang2, Shyh-Chang Chen3, Yen-Ming Lee6, Tzu-An Liu2, Tzu-Ching Chang278, John Wang3, Song-Kun Shyue6, Li-Ying Sung1* and Jun-Yang Liou29*

Author Affiliations

1 Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan

2 Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan 350, Taiwan

3 Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan

4 Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan

5 Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan

6 Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan

7 Graduate Institute of Clinical Medical Science, China Medical University, Taichung 404, Taiwan

8 Metabolomic Medicine Research Center, China Medical University, Taichung 404, Taiwan

9 Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan

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BMC Cancer 2014, 14:425  doi:10.1186/1471-2407-14-425

Published: 12 June 2014

Abstract

Background

14-3-3σ is implicated in promoting tumor development of various malignancies. However, the clinical relevance of 14-3-3σ in hepatocellular carcinoma (HCC) tumor progression and modulation and pathway elucidation remain unclear.

Methods

We investigated 14-3-3σ expression in 109 HCC tissues by immunohistochemistry. Overexpression and knockdown experiments were performed by transfection with cDNA or siRNA. Protein expression and cell migration were determined by Western blot and Boyden chamber assay.

Results

In this study, we found that 14-3-3σ is abundantly expressed in HCC tumors. Stable or transient overexpression of 14-3-3σ induces the expression of heat shock factor-1α (HSF-1α) and heat shock protein 70 (HSP70) in HCC cells. Moreover, expression of 14-3-3σ significantly correlates with HSF-1α/HSP70 in HCC tumors and both 14-3-3σ and HSP70 overexpression are associated with micro-vascular thrombi in HCC patients, suggesting that 14-3-3σ/HSP70 expression is potentially involved in cell migration/invasion. Results of an in vitro migration assay indicate that 14-3-3σ promotes cell migration and that 14-3-3σ-induced cell migration is impaired by siRNA knockdown of HSP70. Finally, 14-3-3σ-induced HSF-1α/HSP70 expression is abolished by the knockdown of β-catenin or activation of GSK-3β.

Conclusions

Our findings indicate that 14-3-3σ participates in promoting HCC cell migration and tumor development via β-catenin/HSF-1α/HSP70 pathway regulation. Thus, 14-3-3σ alone or combined with HSP70 are potential prognostic biomarkers for HCC.

Keywords:
14-3-3σ; β-catenin; Hepatocellular carcinoma; HSF-1; HSP70