title: Mortalin promotes cell proliferation and epithelial mesenchymal transition of intrahepatic cholangiocarcinoma cells in vitro.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.|Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Kang
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Jia-Bin
authors.initials: JB
authors.lastname: Cai
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Rui-Zhao
authors.initials: RZ
authors.lastname: Dong
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Liu
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Xie
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, P.R. China.
authors.forename: Zheng-Ji
authors.initials: ZJ
authors.lastname: Song
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Zhao-Ru
authors.initials: ZR
authors.lastname: Dong
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Mei-Yu
authors.initials: MY
authors.lastname: Hu
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Huang
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Ai-Wu
authors.initials: AW
authors.lastname: Ke
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Guo-Ming
authors.initials: GM
authors.lastname: Shi
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001650:Bile Duct Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D018281:Cholangiocarcinoma / Q000473:pathology*; D015536:Down-Regulation / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D055785:Gene Knockdown Techniques; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D011379:Prognosis; D034741:RNA, Small Interfering / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018840:HSP70 Heat-Shock Proteins; D034741:RNA, Small Interfering; C080352:mortalin
keywords: CANCER RESEARCH; MALIGNANT TUMOURS; METASTASIS