title: Hyperglycemia Promotes Human Gastric Carcinoma Progression via Aquaporin 3.
abstract: BACKGROUND
  Hyperglycemia plays an important role in the development of gastric carcinoma (GC). Aquaporin 3 (AQP3) is overexpressed in GC and involved in carcinogenesis and progression of GC. Hyperglycemia promotes AQP3 expression in human peritoneal mesothelial cells.
  
  
  OBJECTIVE
  To investigate whether hyperglycemia promotes progression of GC via AQP3.
  
  
  METHODS
  We enrolled 978 patients with GC and evaluated the correlation between preoperative fasting plasma glucose and clinicopathological features. AQP3 was detected by immunohistochemistry in human GC specimens. Western blotting and real-time quantitative polymerase chain reaction evaluated changes in AQP3 expression in human GC MGC803 and SGC7901 cells after co-culture with high glucose. Transwell migration and Cell Counting Kit-8 assays were used to determine migration and proliferation of GC cells.
  
  
  RESULTS
  Hyperglycemia (fasting plasma glucose ≥6.1 mM) correlated with tumor size, location, and pTNM stage. AQP3 expression in tumor tissue was associated with fasting plasma glucose levels. High glucose concentration upregulated AQP3 expression in a dose- and time-dependent manner. High glucose concentration promoted GC cell migration markedly, and AQP3 knockdown with siRNA could abolish the increase in cell migration. However, high glucose concentration inhibited cell proliferation, and AQP3 knockdown significantly enhanced the inhibitory effect of high glucose. The ERK and PI3K/AKT signaling pathways were involved in high glucose regulation of AQP3 in human GC cells.
  
  
  CONCLUSIONS
  Hyperglycemia promotes GC progress via AQP3. This improves our understanding of the mechanism of hyperglycemia-induced carcinogenesis and provides a potential therapeutic strategy for GC.
authors.affiliation: Division of Gastrointestinal Surgery, Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China, zhouyang.chun@163.com.
authors.forename: Yangchun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Shoulin
authors.initials: S
authors.lastname: Wang
authors.forename: Lizong
authors.initials: L
authors.lastname: Shen
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D051400:Aquaporin 3 / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D003920:Diabetes Mellitus / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology
chemical_list: D051400:Aquaporin 3