Summary of Study ST000159

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000138. The data can be accessed directly via it's Project DOI: 10.21228/M84G67 This work is supported by NIH grant, U2C- DK119886.


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Study IDST000159
Study TitleU13C-Glutamine and U13C-Glucose Flux Analysis (MFA SiHa B16F10)
Study Type13C mass isotopomer analysis (LCMS flux studies)
Study SummaryOxygenated cancer cells have a high metabolic plasticity as they can use glucose, glutamine and lactate as main substrates to support their bioenergetic and biosynthetic activities. Metabolic optimization requires integration. While glycolysis and glutaminolysis can cooperate to support cellular proliferation, oxidative lactate metabolism opposes glycolysis in oxidative cancer cells engaged in a symbiotic relation with their hypoxic/glycolytic neighbors. However, little is known concerning the relationship between oxidative lactate metabolism and glutamine metabolism. Using SiHa and HeLa human cancer cells, this study reports that intracellular lactate signaling promotes glutamine uptake and metabolism in oxidative cancer cells. It depends on the uptake of extracellular lactate by monocarboxylate transporter 1 (MCT1). Lactate first stabilizes hypoxia-inducible factor-2α (HIF-2α), and HIF-2α then transactivates c-Myc in a pathway that mimics a response to hypoxia. Consequently, lactate-induced c-Myc activation triggers the expression of glutamine transporter ASCT2 and of glutaminase 1 (GLS1), resulting in improved glutamine uptake and catabolism. Elucidation of this metabolic dependence could be of therapeutic interest. First, inhibitors of lactate uptake targeting MCT1 are currently entering clinical trials. They have the potential to indirectly repress glutaminolysis. Second, in oxidative cancer cells, resistance to glutaminolysis inhibition could arise from compensation by oxidative lactate metabolism and increased lactate. Research is published, core data not used in publication but project description is relevant:
University of Michigan
DepartmentBiomedical Research Core Facilities
LaboratoryMetabolomics core
Last NameKachman
First NameMaureen
Address6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Submit Date2014-12-02
Num Groups6
Total Subjects30
Raw Data AvailableYes
Raw Data File Type(s)d
Uploaded File Size1.1 G
Analysis Type DetailLC-MS
Release Date2015-04-28
Release Version1
Maureen Kachman Maureen Kachman application/zip

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Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Condition Labeling
SA008547S00016847Control group 1 U13CGlutamine
SA008548S00016850Control group 1 U13CGlutamine
SA008549S00016851Control group 1 U13CGlutamine
SA008550S00016849Control group 1 U13CGlutamine
SA008551S00016848Control group 1 U13CGlutamine
SA008552S00016858Control line group 2 U13CGlucose
SA008553S00016859Control line group 2 U13CGlucose
SA008554S00016860Control line group 2 U13CGlucose
SA008555S00016857Control line group 2 U13CGlucose
SA008556S00016861Control line group 2 U13CGlucose
SA008557S00016867Control line group 3 U13CGlucose
SA008558S00016868Control line group 3 U13CGlucose
SA008559S00016869Control line group 3 U13CGlucose
SA008560S00016871Control line group 3 U13CGlucose
SA008561S00016870Control line group 3 U13CGlucose
SA008562S00016865Selected line group 2 U13CGlucose
SA008563S00016864Selected line group 2 U13CGlucose
SA008564S00016866Selected line group 2 U13CGlucose
SA008565S00016863Selected line group 2 U13CGlucose
SA008566S00016862Selected line group 2 U13CGlucose
SA008567S00016873Selected line group 3 U13CGlucose
SA008568S00016874Selected line group 3 U13CGlucose
SA008569S00016875Selected line group 3 U13CGlucose
SA008570S00016876Selected line group 3 U13CGlucose
SA008571S00016872Selected line group 3 U13CGlucose
SA008572S00016854Treated group 1 U13CGlutamine
SA008573S00016856Treated group 1 U13CGlutamine
SA008574S00016852Treated group 1 U13CGlutamine
SA008575S00016853Treated group 1 U13CGlutamine
SA008576S00016855Treated group 1 U13CGlutamine
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