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Molecular link between glucose and glutamine consumption in cancer cells mediated by CtBP and SIRT4
Wang, Li1; Li, Jing-jiag1; Guo, Li-yu2; Li, Peipei1; Zhao, Zhiqiang1; Zhou, Haisheng2; Di, Li-jun1
2018-03
Source PublicationONCOGENESIS
ISSN2157-9024
Volume7
Abstract

Glucose and Glutamine are two essential ingredients for cell growth. 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 indicated 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 hypothesized 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 level of glucose but not low glucose level. Low level of glucose supply was found to decrease GDH activity via blocking CtBP dimerization. Mechanically, low glucose also abolished CtBP binding to SIRT4 promoter and the repression of SIRT4 expression. Consistently, the CtBP dimerization inhibitor MTOB mimicked low glucose effects on SIRT4 expression, and GDH activity suggest that CtBP requires high glucose supply to act as a suppressor of SIRT4 gene. In conclusion, we propose that a general molecular pathway composed by CtBP-SIRT4-GDH coordinating the metabolism of glucose and glutamine in cancer cells.

DOI10.1038/s41389-018-0036-8
URLView the original
Indexed BySCI
Language英语
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000429470100003
PublisherNATURE PUBLISHING GROUP
The Source to ArticleWOS
Fulltext Access
Citation statistics
Cited Times [WOS]:18   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Faculty of Health Sciences, University of Macau, Macau, People’s Republic of China
2.Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, 230032 China
First Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Wang, Li,Li, Jing-jiag,Guo, Li-yu,et al. Molecular link between glucose and glutamine consumption in cancer cells mediated by CtBP and SIRT4[J]. ONCOGENESIS,2018,7.
APA Wang, Li.,Li, Jing-jiag.,Guo, Li-yu.,Li, Peipei.,Zhao, Zhiqiang.,...&Di, Li-jun.(2018).Molecular link between glucose and glutamine consumption in cancer cells mediated by CtBP and SIRT4.ONCOGENESIS,7.
MLA Wang, Li,et al."Molecular link between glucose and glutamine consumption in cancer cells mediated by CtBP and SIRT4".ONCOGENESIS 7(2018).
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