title: ZEB2 promotes the metastasis of gastric cancer and modulates epithelial mesenchymal transition of gastric cancer cells.
abstract: BACKGROUND
  Invasion and metastasis are the hallmarks of advanced gastric cancer progression. Therefore, it is urgent to overcome metastasis in order to improve the survival of gastric cancer patients.
  
  
  OBJECTIVE
  This study aimed to examine the expression of ZEB2 in gastric cancer samples and analyze its correlation with clinicopathologic features. In addition, the molecular mechanism by which ZEB2 contributes to gastric cancer metastasis will be explored.
  
  
  METHODS
  ZEB2 expression in clinical gastric cancer samples was evaluated by immunohistochemical analysis. ZEB2 was knocked-down in HGC27 gastric cancer cells by shRNA and the effects on cell invasion and migration were examined by in vitro cell invasion and migration assays. The expression of epithelial marker E-cadherin, mesenchymal markers fibronecin and vimentin, and MMPs was detected by western blot analysis.
  
  
  RESULTS
  The expression of ZEB2 was positively correlated with the depth of invasion, lymph node metastasis and TNM stage. In addition, patients with positive ZEB2 expression showed a significantly shorter overall survival time than did patients with negative ZEB2. shRNA mediated knockdown of ZEB2 resulted in reduced invasion and migration of HGC27 cells, along with the upregulation of E-cadherin and downregulation of fibronecin, vimentin, MMP2, and MMP9.
  
  
  CONCLUSIONS
  ZEB2 expression is closely associated with the clinicopathological parameters of gastric cancer. ZEB2 promotes gastric cancer cell migration and invasion at least partly via the regulation of epithelial-mesenchymal transition. ZEB2 is a potential target for gene therapy of aggressive gastric cancer.
authors.affiliation: Department of Gastroenterology, Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China.
authors.forename: Ying-Huan
authors.initials: YH
authors.lastname: Dai
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Tang
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Zhu
authors.forename: Liang
authors.initials: L
authors.lastname: Lv
authors.forename: Yi
authors.initials: Y
authors.lastname: Chu
authors.forename: Yu-Qian
authors.initials: YQ
authors.lastname: Zhou
authors.forename: Ji-Rong
authors.initials: JR
authors.lastname: Huo
mesh_terms: D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis; D014746:Vimentin / Q000378:metabolism; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D015820:Cadherins; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D014746:Vimentin; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D020782:Matrix Metalloproteinases