title: Effects of nicotinamide N-methyltransferase on PANC-1 cells proliferation, metastatic potential and survival under metabolic stress.
abstract: BACKGROUND
  Aberrant expression of Nicotinamide N-methyltransferase (NNMT) has been reported in pancreatic cancer. However, the role of NNMT in pancreatic cancer development remains elusive. Therefore, the present study was to investigate the impact of NNMT on pancreatic cancer cell proliferation, metastatic potential and survival under metabolic stress.
  
  
  METHODS
  Pancreatic cancer cell line PANC-1 was transfected with NNMT expression plasmid or small interfering RNA of NNMT to overexpress or knockdown intracellular NNMT expression, respectively. Rate of cell proliferation was monitored. Transwell migration and matrigel invasion assays were conducted to assess cell migration and invasion capacity. Resistance to glucose deprivation, sensitivity to glycolytic inhibition, mitochondrial inhibtion and resistance to rapamycin were examined to evaluate cell survival under metabolic stress.
  
  
  RESULTS
  NNMT silencing markedly reduced cell proliferation, whereas NNMT overexpression promoted cell growth moderately. Knocking down NNMT also significantly suppressed the migration and invasion capacities of PANC-1 cells. Conversely, NNMT upregulation enhanced cell migration and invasion capacities. In addition, NNMT knockdown cells were much less resistant to glucose deprivation and rapamycin as well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-expressing cells showed opposite effects although the effects were not so striking.
  
  
  CONCLUSIONS
  These data sugguest that NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Yong-Tao
authors.initials: YT
authors.lastname: Wang
authors.forename: Pan
authors.initials: P
authors.lastname: Chen
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Li
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Chen
authors.forename: Hang
authors.initials: H
authors.lastname: Zeng
authors.forename: Ai-Ming
authors.initials: AM
authors.lastname: Yu
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Hui-Chang
authors.initials: HC
authors.lastname: Bi
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D055785:Gene Knockdown Techniques; D006801:Humans; D050903:Nicotinamide N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D013312:Stress, Physiological; D014162:Transfection; D015854:Up-Regulation
chemical_list: C494406:NNMT protein, human; D050903:Nicotinamide N-Methyltransferase