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 language | English (US) |
|---|---|
| Pages (from-to) | 3536-3546 |
| Number of pages | 11 |
| Journal | Journal of proteome research |
| Volume | 16 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 6 2017 |
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Keywords
- Cancer metabolism
- Glucose limitation
- Glutamine metabolism
- MUC1 overexpression
- NMR metabolomics
ASJC Scopus subject areas
- Biochemistry
- Chemistry(all)
Cite this
Glucose limitation alters glutamine metabolism in MUC1- overexpressing pancreatic cancer cells. / Gebregiworgis, Teklab; Purohit, Vinee; Shukla, Surendra K.; Tadros, Saber; Chaika, Nina V.; Abrego, Jaime; Mulder, Scott E.; Gunda, Venugopal; Singh, Pankaj; Powers, Robert.
In: Journal of proteome research, Vol. 16, No. 10, 06.10.2017, p. 3536-3546.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glucose limitation alters glutamine metabolism in MUC1- overexpressing pancreatic cancer cells
AU - Gebregiworgis, Teklab
AU - Purohit, Vinee
AU - Shukla, Surendra K.
AU - Tadros, Saber
AU - Chaika, Nina V.
AU - Abrego, Jaime
AU - Mulder, Scott E.
AU - Gunda, Venugopal
AU - Singh, Pankaj
AU - Powers, Robert
PY - 2017/10/6
Y1 - 2017/10/6
N2 - 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.
AB - 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.
KW - Cancer metabolism
KW - Glucose limitation
KW - Glutamine metabolism
KW - MUC1 overexpression
KW - NMR metabolomics
UR - http://www.scopus.com/inward/record.url?scp=85042187030&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042187030&partnerID=8YFLogxK
U2 - 10.1021/acs.jproteome.7b00246
DO - 10.1021/acs.jproteome.7b00246
M3 - Article
C2 - 28809118
AN - SCOPUS:85042187030
VL - 16
SP - 3536
EP - 3546
JO - Journal of Proteome Research
JF - Journal of Proteome Research
SN - 1535-3893
IS - 10
ER -