title: Metformin inhibits esophagus cancer proliferation through upregulation of USP7.
abstract: BACKGROUND
  Recent population studies suggest that the use of metformin is associated with reduced incidence and improved prognosis of certain cancers.
  
  
  METHODS
  In the current study, we assessed the effect of metformin on esophagus cancer cells using two cell lines (Eca-109 and TE-1 cells).
  
  
  RESULTS
  We found that metformin inhibited growth and decreased expression of cell-cycle regulators in these cells. Treatment with metformin was also associated with activation of AMP kinase and inhibition of mTOR/p70S6K/pS6 signaling in both cells. However, inhibition of AMPK signaling has little impact on the anti-proliferative roles of metformin. In addition, we found USP7, a positive regulator of tumor suppressor p53, as a new molecular target of metformin. Esophagus cancer cells can be protected against metformin-induced growth inhibition by small interfering RNA against USP7.
  
  
  CONCLUSIONS
  These results provide evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent population studies and justify further work to explore potential roles for it in esophagus cancer prevention and treatment.
authors: Department of Shanghai Lung Tumor Clinic Medical Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Yunhua
authors: Y
authors: Xu
authors: Shun
authors: S
authors: Lu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008687:Metformin / Q000494:pharmacology*; D055550:Protein Stability / Q000187:drug effects; D034741:RNA, Small Interfering; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D000076084:Ubiquitin-Specific Peptidase 7; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C530104:CCND1 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D034741:RNA, Small Interfering; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D008687:Metformin; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7