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PMID: 28915621 Published · epublish English Journal Article

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

Oncotarget ·Vol. 8 ·No. 34 ·2017-08-22 ·Pages 56672-56683

Liu S, Jiang B, Li H, He Z, Lv P, Peng C, Wang Y, Cheng W, Xu Z, Chen W, Liu Z, Zhang B, Shen S, Xiang S

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.

Keywords
MMP-2 Wip1 intrahepatic cholangiocarcinoma prognosis
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Liu Sulai
Department 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.
Jiang Bo
Department 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.
Li Hao
Department 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.
He Zili
Department 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.
Lv Pin
Department 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.
Peng Chuang
Department 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.
Wang Yonggang
Department 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.
Cheng Wei
Department 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.
Xu Zhengquan
Department of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, People's Republic of China.
Chen Wei
Department of Thoracic, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People's Republic of China.
Liu Zhengkai
Department 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.
Zhang Bao
Department 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.
Shen Shengqian
Department 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.
Xiang Shuanglin
Key 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.
Conflict of Interest

CONFLICTS OF INTEREST The authors declare that they have no financial or commercial conflicts of interest.

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Article Info
Journal
Oncotarget
Abbr.
Oncotarget
ISSN
1949-2553
DOI
10.18632/oncotarget.18074
Published
2017-08-22
Epub
2017-00-23
Pages
56672-56683
Language
English
Region
United States
NLM ID
101532965
PMCID
PMC5593592
External Links
PubMed source DOI: 10.18632/oncotarget.18074 PMC Full Text View journal details
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