Oncotarget

Research Papers:

Wip1 is associated with tumorigenity and metastasis through MMP-2 in human intrahepatic cholangiocarcinoma

Sulai Liu, Bo Jiang _, Hao Li, Zili He, Pin Lv, Chuang Peng, Yonggang Wang, Wei Cheng, Zhengquan Xu, Wei Chen, Zhengkai Liu, Bao Zhang, Shengqian Shen and Shuanglin Xiang

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Oncotarget. 2017; 8:56672-56683. https://doi.org/10.18632/oncotarget.18074

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Abstract

Sulai Liu1, Bo Jiang1, Hao Li1, Zili He1, Pin Lv1, Chuang Peng1, Yonggang Wang1, Wei Cheng1, Zhengquan Xu2, Wei Chen3, Zhengkai Liu1, Bao Zhang1, Shengqian Shen1 and Shuanglin Xiang4

1Department of Hepatobiliary Surgery/Hunan Research Center of Biliary Disease, Hunan Provincial People’s Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People’s Republic of China

2Department of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China

3Department of Thoracic, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China

4Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan Province, People’s Republic of China

Correspondence to:

Bo Jiang, email: [email protected]

Keywords: intrahepatic cholangiocarcinoma, Wip1, MMP-2, prognosis

Received: March 26, 2017    Accepted: April 26, 2017    Published: May 23, 2017

ABSTRACT

Wip1 has been shown to correlate with the metastasis/invasion of several tumors. This study was designed to investigate the clinical significance and biological function of Wip1 in intrahepatic cholangiocarcinoma (ICC). The expression of Wip1 was investigated in sixty human ICC biopsy samples by immunohistochemistry. Transient and stable knockdown of Wip1 in two human ICC cells (ICC-9810 and SSP25) were established using short hairpin RNA expression vector. Immunohistochemistry revealed that Wip1 was up-regulated in human ICC tissues (47/60, 78.3%). High levels of Wip1 in human ICC correlated with metastasis to the lymph metastasis (P=0.022). Genetic depletion of Wip1 in ICC cells resulted in significantly inhibited proliferation and invasion compared with controls. Most importantly, Wip1 down-regulation impaired tumor migration capacity of ICC cells in vivo. Subsequent investigations revealed that matrix metalloproteinase-2 (MMP-2) is an important target of Wip1. Consistently, in human ICC tissues, Wip1 level was positively correlated with MMP-2 expression. Taken together, our founding indicates that Wip1 may be a crucial regulator in the tumorigenicity and invasion of human ICC, Wip1 exerts its pro-invasion function at least in part through the MMP-2 signaling pathway, suggesting Wip1 as a potential therapeutic target for ICC.


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