title: Metadherin promotes hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition.
abstract: OBJECTIVE
  To investigate the expression of metadherin (MTDH) for its prognostic value in hepatocellular carcinoma (HCC) and its role in promoting HCC metastasis.
  
  
  METHODS
  This study employed a tissue microarray containing samples from 323 HCC patients to examine the expression of MTDH and its correlation with other clinicopathologic characteristics. The role of MTDH in the regulation of HCC metastasis was investigated both in vitro and in vivo using short hairpin RNA (shRNA)-mediated downregulation of MTDH in HCC cell lines with various metastatic potentials.
  
  
  RESULTS
  The expression of MTDH was markedly higher in HCC tumors than in normal liver tissue. Particularly high MTDH expression was observed in tumors with microvascular invasion, pathologic satellites, poor differentiation, or tumor-node-metastasis stages II to III. Furthermore, the clinical outcome was consistently poorer for the MTDH(high) group than for the MTDH(low) group in the 1-, 3-, and 5-year overall survival (OS) rates and in the 1-, 3-, 5-year cumulative recurrence rates. In a nude mice model, the shRNA-mediated downregulation of MTDH resulted in a reduced migratory capacity in HCC cell lines, as well as a reduction in pulmonary and abdominal metastasis. Furthermore, we found that the expression level of MTDH correlated with four epithelial-mesenchymal transition (EMT) markers. Knockdown of MTDH expression in HCC cell lines resulted in downregulation of N-cadherin and snail, upregulation of E-cadherin, and translocation of β-catenin.
  
  
  CONCLUSIONS
  MTDH may promote HCC metastasis through the induction of EMT process and may be a candidate biomarker for prognosis as well as a target for therapy.
authors: Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai, China.
authors: Kai
authors: K
authors: Zhu
authors: Zhi
authors: Z
authors: Dai
authors: Qi
authors: Q
authors: Pan
authors: Zheng
authors: Z
authors: Wang
authors: Guo-Huan
authors: GH
authors: Yang
authors: Lei
authors: L
authors: Yu
authors: Zhen-Bin
authors: ZB
authors: Ding
authors: Guo-Ming
authors: GM
authors: Shi
authors: Ai-Wu
authors: AW
authors: Ke
authors: Xin-Rong
authors: XR
authors: Yang
authors: Zhong-Hua
authors: ZH
authors: Tao
authors: Yi-Ming
authors: YM
authors: Zhao
authors: Yi
authors: Y
authors: Qin
authors: Hai-Ying
authors: HY
authors: Zeng
authors: Zhao-You
authors: ZY
authors: Tang
authors: Jia
authors: J
authors: Fan
authors: Jian
authors: J
authors: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D040081:Protein Array Analysis; D034622:RNA Interference; D016601:RNA-Binding Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis; D051176:beta Catenin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; C483038:Mtdh protein, mouse; D016601:RNA-Binding Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051176:beta Catenin