title: The transcription factor FOXO4 is down-regulated and inhibits tumor proliferation and metastasis in gastric cancer.
abstract: BACKGROUND
  FOXO4, a member of the FOXO family of transcription factors, is currently the focus of intense study. Its role and function in gastric cancer have not been fully elucidated. The present study was aimed to investigate the expression profile of FOXO4 in gastric cancer and the effect of FOXO4 on cancer cell growth and metastasis.
  
  
  METHODS
  Immunohistochemistry, Western blotting and qRT-PCR were performed to detect the FOXO4 expression in gastric cancer cells and tissues. Cell biological assays, subcutaneous tumorigenicity and tail vein metastatic assay in combination with lentivirus construction were performed to detect the impact of FOXO4 to gastric cancer in proliferation and metastasis in vitro and in vivo. Confocal and qRT-PCR were performed to explore the mechanisms.
  
  
  RESULTS
  We found that the expression of FOXO4 was decreased significantly in most gastric cancer tissues and in various human gastric cancer cell lines. Up-regulating FOXO4 inhibited the growth and metastasis of gastric cancer cell lines in vitro and led to dramatic attenuation of tumor growth, and liver and lung metastasis in vivo, whereas down-regulating FOXO4 with specific siRNAs promoted the growth and metastasis of gastric cancer cell lines. Furthermore, we found that up-regulating FOXO4 could induce significant G1 arrest and S phase reduction and down-regulation of the expression of vimentin.
  
  
  CONCLUSIONS
  Our data suggest that loss of FOXO4 expression contributes to gastric cancer growth and metastasis, and it may serve as a potential therapeutic target for gastric cancer.
authors.forename: Linna
authors.initials: L
authors.lastname: Su
authors.forename: Xiangqiang
authors.initials: X
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Chai
authors.forename: Lifen
authors.initials: L
authors.lastname: Lv
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Xiaosa
authors.initials: X
authors.lastname: Li
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 127 Changle Western Road, Xi'an, Shaanxi Province 710032, People's Republic of China. shiyquan@fmmu.edu.cn.
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Shi
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D018797:Cell Cycle Proteins; C108803:FOXO4 protein, human; D051858:Forkhead Transcription Factors; D014157:Transcription Factors