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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2016

Open Access 01-12-2016 | Research

Prohibitin overexpression predicts poor prognosis and promotes cell proliferation and invasion through ERK pathway activation in gallbladder cancer

Authors: Yang Cao, Haibin Liang, Fei Zhang, Zhou Luan, Shuai Zhao, Xu-an Wang, Shibo Liu, Runfa Bao, Yijun Shu, Qiang Ma, Jian Zhu, Yingbin Liu

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2016

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Abstract

Background

Prohibitin (PHB), a pleiotropic protein overexpressed in several tumor types, has been implicated in the regulation of cell proliferation, invasive migration and survival. However, PHB expression and its biological function in gallbladder cancer (GBC) remain largely unknown.

Methods

PHB and p-ERK protein expressions were determined in human GBC tissues by immunohistochemistry (IHC). The effects of PHB knockdown on GBC cell proliferation and invasiveness were evaluated using Cell Counting Kit-8 (CCK-8) cell viability, cell cycle analysis, transwell invasion and gelatin zymography assays. Subcutaneous xenograft and tail vein-lung metastasis tumor models in nude mice were employed to further substantiate the role of PHB in GBC progression.

Results

PHB protein was overexpressed in GBC tissues and was significantly associated with histological grade, tumor stage and perineural invasion. Furthermore, PHB expression was negatively associated with overall survival in GBC patients. In vitro experimental studies demonstrated that the downregulation of PHB expression by lentivirus-mediated shRNA interference not only inhibited the ERK pathway activation but also reduced the proliferative and invasive capacities of GBC cells.
Moreover, PD0325901, a specific inhibitor of MEK, markedly impaired PHB- mediated phosphorylation of ERK protein. IHC statistical analyses further validated that PHB expression was positively correlated with ERK protein phosphorylation levels in GBC tissue samples. In vivo, PHB depletion also resulted in dramatic reductions in the growth and metastasis of GBC cells.

Conclusion

Our findings demonstrate that PHB overexpression predicts poor survival in GBC patients. PHB could serve as a novel prognostic biomarker and a potential therapeutic target for GBCs.
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Metadata
Title
Prohibitin overexpression predicts poor prognosis and promotes cell proliferation and invasion through ERK pathway activation in gallbladder cancer
Authors
Yang Cao
Haibin Liang
Fei Zhang
Zhou Luan
Shuai Zhao
Xu-an Wang
Shibo Liu
Runfa Bao
Yijun Shu
Qiang Ma
Jian Zhu
Yingbin Liu
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2016
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-016-0346-7

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