title: Aberrant expression of GATA binding protein 6 correlates with poor prognosis and promotes metastasis in cholangiocarcinoma.
abstract: OBJECTIVE
  GATA6, a zinc-finger transcription factor, functions as a tumour promoter or suppresser according to different tumour origins. We investigated the clinical significance of GATA6 and its role in invasion and metastasis in cholangiocarcinoma (CCA).
  
  
  METHODS
  Expression of GATA6 in 87 cancerous, 24 paracancerous, 32 lymph-node metastatic and 8 liver metastatic samples from 87 CCA patients undergoing surgical resection was detected by immunohistochemistry. Impact of GATA6 on invasion, metastasis and 67kDa laminin receptor expression (67LR) was evaluated in CCA cells by shRNA lentivirus or expressed-plasmid transfection.
  
  
  RESULTS
  Aberrant expression of GATA6 in CCAs was significantly associated with lymph-node metastasis. GATA6 expression was higher in lymph-node and liver metastatic tissues compared with primary cancerous tissues. Kaplan-Meier analysis showed GATA6 expression correlated with poor overall survival and early recurrence in CCAs. Cox analysis suggested GATA6 was an independent prognostic marker for overall survival and recurrence-free survival. CCA cell invasion and migration were decreased by GATA6 knockdown and enhanced by GATA6 overexpression in vitro. Knockdown of GATA6 reduced CCA cell metastasis by xenotransplantation into nude mice. 67LR, which is overexpressed in CCAs and promotes invasion and metastasis through several pathways, positively correlated with GATA6 expression in 87 CCAs. Both mRNA and protein levels of 67LR were regulated by GATA6 in CCA cells. Moreover, ChIP analysis showed GATA6 bound to 67LR gene promoter in CCA cells.
  
  
  CONCLUSIONS
  Aberrant expression of GATA6 correlates with poor prognosis and promotes invasion and metastasis in CCA.
authors: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Feng
authors: F
authors: Tian
authors: Dajiang
authors: D
authors: Li
authors: Jian
authors: J
authors: Chen
authors: Wei
authors: W
authors: Liu
authors: Lei
authors: L
authors: Cai
authors: Jianwei
authors: J
authors: Li
authors: Peng
authors: P
authors: Jiang
authors: Zipei
authors: Z
authors: Liu
authors: Xin
authors: X
authors: Zhao
authors: Fei
authors: F
authors: Guo
authors: Xiaowu
authors: X
authors: Li
authors: Shuguang
authors: S
authors: Wang
mesh_terms: D000368:Aged; D000818:Animals; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D016016:Proportional Hazards Models; D011485:Protein Binding; D034622:RNA Interference; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; C510624:RPSA protein, human; D017474:Receptors, Laminin; D012269:Ribosomal Proteins