Effects of nicotinamide n-methyltransferase on PANC-1 cells proliferation, metastatic potential and survival under metabolic stress

Tao Yu, Yong Tao Wang, Pan Chen, Yu Hua Li, Yi Xin Chen, Hang Zeng, Aiming Yu, Min Huang, Hui Chang Bi

Research output: Contribution to journalArticle

27 Scopus citations

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. Conclusion: These data sugguest that NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress.

Original languageEnglish (US)
Pages (from-to)710-721
Number of pages12
JournalCellular Physiology and Biochemistry
Volume35
Issue number2
DOIs
StatePublished - Feb 4 2015

Keywords

  • Invasion
  • Metabolic stress
  • Migration
  • NNMT
  • PANC-1
  • Proliferation

ASJC Scopus subject areas

  • Physiology

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