title: Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is a rapidly growing tumor associated with a high propensity for vascular invasion and metastasis. Epithelial-mesenchymal transition (EMT) is a key event in the tumor invasion process. Recently, Twist has been identified to play an important role in EMT-mediated metastasis through the regulation of E-cadherin expression. However, the actual role of Twist in tumor invasiveness remains unclear. The purpose of this study is to investigate the expression and possible role of Twist in HCC.
  
  
  METHODS
  We evaluated Twist and E-cadherin expression in HCC tissue microarray of paired primary and metastatic HCC by immunohistochemical staining. The role of Twist in EMT-mediated invasiveness was also evaluated in vitro in HCC cell lines.
  
  
  RESULTS
  We first showed that overexpression of Twist was correlated with HCC metastasis (P=0.001) and its expression was negatively correlated with E-cadherin expression (P=0.001, r=-0.443) by tissue microarray. A significant increase of Twist at the mRNA level was also found in metastatic HCC cell lines MHCC-97H, MHCC-97L, and H2M when compared with nonmetastatic Huh-7, H2P, and PLC cell lines. The MHCC-97H cell line, which has a higher metastatic ability, was found to have a higher level of Twist than MHCC-97L. Accompanied with increased Twist expression in the metastatic HCC cell lines when compared with the nonmetastatic primary ones, we found decreased E-cadherin mRNA expression in the metastatic HCC cell lines. By ectopic transfection of Twist into PLC cells, Twist was able to suppress E-cadherin expression and induce EMT changes, which was correlated with increased HCC cell invasiveness.
  
  
  CONCLUSIONS
  This study shows that Twist overexpression was correlated with HCC metastasis through induction of EMT changes and HCC cell invasiveness.
authors.affiliation: Centre for the Study of Liver Disease, and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Terence K
authors.initials: TK
authors.lastname: Lee
authors.forename: Ronnie T P
authors.initials: RT
authors.lastname: Poon
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Yuen
authors.forename: Ming Tat
authors.initials: MT
authors.lastname: Ling
authors.forename: Wei Kei
authors.initials: WK
authors.lastname: Kwok
authors.forename: Xiang Hong
authors.initials: XH
authors.lastname: Wang
authors.forename: Yong Chuan
authors.initials: YC
authors.lastname: Wong
authors.forename: Xin Yuan
authors.initials: XY
authors.lastname: Guan
authors.forename: Kwan
authors.initials: K
authors.lastname: Man
authors.forename: King Lok
authors.initials: KL
authors.lastname: Chau
authors.forename: Sheung Tat
authors.initials: ST
authors.lastname: Fan
mesh_terms: D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D046228:Microarray Analysis / Q000379:methods; D009361:Neoplasm Invasiveness / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D013223:Statistics as Topic; D015533:Transcriptional Activation / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015820:Cadherins; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1