Glucose limitation alters glutamine metabolism in MUC1- overexpressing pancreatic cancer cells

Teklab Gebregiworgis, Vinee Purohit, Surendra K. Shukla, Saber Tadros, Nina V. Chaika, Jaime Abrego, Scott E. Mulder, Venugopal Gunda, Pankaj K. Singh, Robert Powers

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Pancreatic cancer cells overexpressing Mucin 1 (MUC1) rely on aerobic glycolysis and, correspondingly, are dependent on glucose for survival. Our NMR metabolomics comparative analysis of control (S2-013.Neo) and MUC1-overexpressing (S2-013.MUC1) cells demonstrates that MUC1 reprograms glutamine metabolism upon glucose limitation. The observed alteration in glutamine metabolism under glucose limitation was accompanied by a relative decrease in the proliferation of MUC1-overexpressing cells compared with steady-state conditions. Moreover, glucose limitation induces G1 phase arrest where S2-013.MUC1 cells fail to enter S phase and synthesize DNA because of a significant disruption in pyrimidine nucleotide biosynthesis. Our metabolomics analysis indicates that glutamine is the major source of oxaloacetate in S2-013.Neo and S2-013.MUC1 cells, where oxaloacetate is converted to aspartate, an important metabolite for pyrimidine nucleotide biosynthesis. However, glucose limitation impedes the flow of glutamine carbons into the pyrimidine nucleotide rings and instead leads to a significant accumulation of glutamine-derived aspartate in S2-013.MUC1 cells.

Original languageEnglish (US)
Pages (from-to)3536-3546
Number of pages11
JournalJournal of proteome research
Volume16
Issue number10
DOIs
StatePublished - Oct 6 2017

Keywords

  • Cancer metabolism
  • Glucose limitation
  • Glutamine metabolism
  • MUC1 overexpression
  • NMR metabolomics

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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    Gebregiworgis, T., Purohit, V., Shukla, S. K., Tadros, S., Chaika, N. V., Abrego, J., Mulder, S. E., Gunda, V., Singh, P. K., & Powers, R. (2017). Glucose limitation alters glutamine metabolism in MUC1- overexpressing pancreatic cancer cells. Journal of proteome research, 16(10), 3536-3546. https://doi.org/10.1021/acs.jproteome.7b00246