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Mortalin promotes cell proliferation and epithelial mesenchymal transition of intrahepatic cholangiocarcinoma cells in vitro
  1. Qiang Kang1,2,
  2. Jia-Bin Cai2,
  3. Rui-Zhao Dong2,
  4. Li-Xin Liu1,
  5. Chi Zhang2,
  6. Peng-Fei Zhang2,
  7. Hao Zou1,
  8. Nan Xie1,
  9. Lu Zhang2,
  10. Xin-Yu Zhang2,
  11. Zheng-Ji Song3,
  12. Zhao-Ru Dong2,
  13. Mei-Yu Hu2,
  14. Xiao-Yong Huang2,
  15. Xiao-Wen Zhang1,
  16. Ai-Wu Ke2,
  17. Guo-Ming Shi2
  1. 1Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
  2. 2Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, P.R. China
  3. 3Department of Gastroenterology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, P.R. China
  1. Correspondence to Dr Guo-Ming Shi, Liver Cancer Institute and Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, P.R. China; shi.guoming{at}zs-hospital.sh.cn OR Dr. Ai-Wu Ke, Liver Cancer Institute and Zhongshan Hospital.sh.cn, ke.aiwu{at}zs-hospital.sh.cn; OR Dr. Xiao-Wen Zhang, Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, 374 Dianmian Road, Kunming, Yunnan, 650101, P.R. China.zhangxiaowenlu{at}hotmail.com.

Abstract

Aims The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) remains poor in terms of overall survival (OS) and recurrence rate. Mortalin, a stress chaperone, has been reported to be involved in carcinogenesis and metastasis. However, its role in ICC has not been defined.

Methods Mortalin expression in tumour samples from patients with ICC was examined by Western blot and immunohistochemistry, and correlation between its expression and clinicopathological features was assessed. In addition, invasion, migration proliferation and apoptosis, and the expression of epithelial-mesenchymal transition (EMT)-related markers in ICC cells were assessed after mortalin depletion. Finally, the prognostic significance of mortalin in patients with ICC was further evaluated by Kaplan–Meier and Cox regression analysis.

Results We provide evidence that expression of mortalin in human ICC tissues is higher than that in matched peritumoural tissues. The interference of mortalin expression inhibited the proliferation and invasion of ICC cells in vitro. Mechanistically, inhibition of mortalin expression in ICC cells upregulated E-cadherin expression and decreased vimentin and snail expression. Clinically, a high level of mortalin in ICC samples was associated with loss of E-cadherin, and increased expression of vimentin and snail. Patients with ICC and high mortalin expression had a shorter OS and a higher recurrence rate. Multivariate analysis revealed that mortalin overexpression was an independent prognostic indicator for patients with ICC.

Conclusions Mortalin may promote cell proliferation and invasion via induction of EMT of ICC cells. A high level of mortalin may be used as a prognostic biomarker and therapeutic target for patients with ICC.

  • MALIGNANT TUMOURS
  • METASTASIS
  • CANCER RESEARCH

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Footnotes

  • QK, J-BC and R-ZD contributed equally.

  • Handling editor Des Richardson

  • Contributors G-MS, X-WZ and A-WK designed the study and modified the manuscript. QK, J-BC and R-ZD did most of the experiments, analysed the data, wrote the manuscript and contributed equally to this work. L-XL, CZ, P-FZ, HZ and NX participated in the IHC staining and analysis. LZ, X-YZ, Z-JS and Z-RD collected clinical data. M-YH and X-YH did the cell cultures. All authors read and approved the final manuscript.

  • Funding This study was supported by the National Natural Science Foundation of China (NSFC-81472840; NSFC-81160062; NSFC-81272295; NSFC-81172023; NSFC-81071741); Shanghai Municipal Natural Science Foundation (14ZR1405800 and 12ZR1402200).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Zhongshan Hospital Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data were available to XWZ and GMS.

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