title: FBXL5 inhibits metastasis of gastric cancer through suppressing Snail1.
abstract: OBJECTIVE
  The Snail family of transcription factors controls epithelial to mesenchymal transition (EMT), a process associated with tumorigenesis originated from epithelial cells. Snail1 is a member from Snail family and upregulation of Snail1 has been detected in gastric cancer (GC), suggesting a potential role of Snail1 in GC metastasis. We have recently reported that FBXL5 regulates cortactin by inducing its ubiquitylation and subsequent proteasomal degradation, resulting in inhibition of metastasis of GC. However, a role of FBXL4 in regulation of other EMT-associated proteins is not unknown.
  
  
  METHODS
  The levels of FBXL5 and Snail1 as well as their relationship were determined in GC specimen. Co-immunoprecipitation (IP) was performed to detect the interaction between Snail1 and FBXL5 in GC cells. The effects on Snail1 by FBXL5 were examined by overexpression of depletion of FBXL5 in GC cells. The invasiveness of the FBXL5-modified GC cells was examined in both scratch wound healing assay and transwell matrix penetration assay.
  
  
  RESULTS
  FBXL5 also physiologically interacted with Snail1. FBXL5 inhibited Snail1 to suppress GC cell invasiveness.
  
  
  CONCLUSIONS
  FBXL5 negatively regulates several EMT-enhancing factors. FBXL5 is an attractive novel target for inhibiting invasion and metastasis of GC cells.
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai JiaoTong University affiliated First People's Hospital (North), Shanghai, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Wu
authors.forename: Honghua
authors.initials: H
authors.lastname: Ding
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.forename: Weihao
authors.initials: W
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D044783:F-Box Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D009362:Neoplasm Metastasis; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D044783:F-Box Proteins; C521741:FBXL5 protein, human; D034741:RNA, Small Interfering; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases