Affiliations: [a] Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery , First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang, China | [b] Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou 310000, Zhejiang, China | [c] Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou 310003, Zhejiang, China | [d] Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Hangzhou 310000, Zhejiang, China
Correspondence:
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Corresponding authors: Shusen Zheng and Jian Wu, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, China. Tel./Fax: +86 0571 87236601; E-mail: shusenzheng@zju.edu.cn;drwujian@hotmail.com.
Note: [1] These authors contributed equally to this work.
Abstract: BACKGROUND: 14-3-3σ protein plays an important role in multiple cellular processes. The role of 14-3-3σ in the progression of intrahepatic cholangiocarcinoma (ICC) has not been well understood. OBJECTIVE: We performed this research to explore the relationship between 14-3-3σ level and clinical characteristics and prognosis of ICC patients. Besides, we used ICC cell lines HCCC-9810 and RBE to assess the biological function of 14-3-3σ. METHODS: We examined 14-3-3σ expression in 28 ICC tissues and matched paratumor tissues by quantitative real-time PCR and immunohistochemistry. Additionally, ICC tissue array from 100 patients and normal liver tissue array from 24 healthy people were also analyzed by immunohistochemistry. 14-3-3σ was knocked down in ICC cell lines and the functions and mechanisms of 14-3-3σ were assessed. RESULTS: 14-3-3σ is highly expressed in ICC tissues and high expression of 14-3-3σ correlates poor overall survival in ICC patients. Knocking down of 14-3-3σ in ICC cell lines reduced cells migration, invasion and anoikis resistance. Furthermore, 14-3-3σ-silenced ICC cells showed significantly decreased invasion-related protein MMP2 and MMP9 expression. CONCLUSIONS:Our results demonstrate prognostic value of 14-3-3σ and its role in metastasis, which is associated with ICC cell lines migration, invasion and anoikis resistance.
