Molecular link between glucose and glutamine consumption in cancer cells mediated by CtBP and SIRT4

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Status	已發表Published
	Molecular link between glucose and glutamine consumption in cancer cells mediated by CtBP and SIRT4
	Wang, L.; Li, JL; Guo, LG; Li, PL; Zhao, ZZ; Zhou, HZ; Di, L.
	2018-03-01
Source Publication	Oncogenesis
ISSN	2157-9024
Pages	1-12
Abstract	Glucose and Glutamine are two most essential ingredients among all types of nutrients and provide the most of carbon and nitrogen sources. However, it remains open for investigation whether there is a general mechanism that coordinates the consumption of glucose and glutamine in cancer cells. Glutamine is mainly metabolized through the glutaminolysis pathway and our previous report indicates that CtBP increases GDH activity and promotes glutaminolysis through repressing the expression of SIRT4, a well-known mitochondrion-located factor that inhibits glutaminolysis pathway. CtBP is known to be a sensor of intracellular metabolic status, we thus hypothesize that a consensus CtBP-SIRT4-GDH axis may mediate the crosstalk between glycolysis and glutaminolysis. Herein, supporting this hypothesis, we observed the coordinated consumption of glucose and glutamine across different cell lines. This coordination was found to be related to CtBP repression activity on SIRT4 expression under high glucose supply but not under low glucose supply which decreased GDH activity via blocking CtBP dimerization to reduce CtBP binding at SIRT4 promoter and release SIRT4 gene expression. Consistently, the result that CtBP dimerization inhibitor, MTOB mimicked low glucose effects on SIRT4 expression and GDH activity suggest that CtBP requires the high glucose metabolism to act as a suppressor of SIRT4 gene to coordinate glucose and glutamine metabolism. In conclusion, we propose that a general molecular pathway composed by CtBP-SIRT4-GDH coordinates the metabolism of glucose and glutamine in cancer cells to affect cell growth.
Keyword	CtBP Sirt4 glucose glutamine
Language	英語English
The Source to Article	PB_Publication
PUB ID	35884
Document Type	Journal article
Collection	DEPARTMENT OF BIOMEDICAL SCIENCES
Recommended Citation GB/T 7714	Wang, L.,Li, JL,Guo, LG,et al. Molecular link between glucose and glutamine consumption in cancer cells mediated by CtBP and SIRT4[J]. Oncogenesis, 2018, 1-12.
APA	Wang, L.., Li, JL., Guo, LG., Li, PL., Zhao, ZZ., Zhou, HZ., & Di, L. (2018). Molecular link between glucose and glutamine consumption in cancer cells mediated by CtBP and SIRT4. Oncogenesis, 1-12.
MLA	Wang, L.,et al."Molecular link between glucose and glutamine consumption in cancer cells mediated by CtBP and SIRT4".Oncogenesis (2018):1-12.

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