title: Reduced expression of DACT2 promotes hepatocellular carcinoma progression: involvement of methylation-mediated gene silencing.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in humans, and its prognosis is generally poor even after surgery. Many advances have been made to understand the pathogenesis of HCC; however, the molecular mechanisms that lead to hepatocarcinogenesis and progression are still not clearly understood.
  
  
  METHODS
  The expression of DACT2 in specimens from 30 paired HCCs and an additional 61 HCC patients after liver transplantation was evaluated by quantitative RT-PCR and immunohistochemical analysis. We investigated the methylation status of the DACT2 promoter region. We also analyzed the alterations of the cell cycle, migration and invasion after DACT2 knockdown.
  
  
  RESULTS
  The expression level of DACT2 was significantly lower in HCC tissues than in non-cancerous tissues. Reduced DACT2 expression was associated with large tumor size. DACT2 transcripts were at low levels in hypermethylated liver cancer cells and were restored by exposure to a demethylating agent. Reduced expression of DACT2 in MHCC97L cells induced G1/S arrest, increased cell proliferation, and promoted cell invasion.
  
  
  CONCLUSIONS
  Our study suggests that DACT2 is silenced by promoter hypermethylation, and reduced DACT2 can promote liver cancer progression. DACT2 may serve as a novel tumor suppressor gene in HCC.
authors.affiliation: Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Gao
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yang
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Zheng
authors.forename: Jia
authors.initials: J
authors.lastname: Yao
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Wu
authors.forename: Hai-Yang
authors.initials: HY
authors.lastname: Xie
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Shu-Sen
authors.initials: SS
authors.lastname: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C478653:DACT2 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger