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Glucose Limitation Alters Glutamine Metabolism in MUC1-Overexpressing Pancreatic Cancer Cells.


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.

SUBMITTER: Gebregiworgis T 

PROVIDER: S-EPMC5634392 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Glucose Limitation Alters Glutamine Metabolism in MUC1-Overexpressing Pancreatic Cancer Cells.

Gebregiworgis Teklab T   Purohit Vinee V   Shukla Surendra K SK   Tadros Saber S   Chaika Nina V NV   Abrego Jaime J   Mulder Scott E SE   Gunda Venugopal V   Singh Pankaj K PK   Powers Robert R  

Journal of proteome research 20170830 10


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 compar  ...[more]

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