Summary of Study ST000159

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, 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: http://www.tandfonline.com/doi/full/10.1080/15384101.2015.1120930
Institute
University of Michigan
DepartmentBiomedical Research Core Facilities
LaboratoryMetabolomics core
Last NameKachman
First NameMaureen
Address6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Email mkachman@umich.edu
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
https://dx.doi.org/10.21228/M84G67
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN000251
Analysis type MS
Chromatography type HILIC
Chromatography system Agilent 1260
Column Phenomenex Luna NH2 (150 x 1mm, 3um)
MS Type ESI
MS instrument type QTOF
MS instrument name Agilent 6520 QTOF
Ion Mode NEGATIVE
Units Area

Chromatography:

Chromatography ID:CH000176
Methods ID:AQM010
Methods Filename:QTOF-002-HILIC-35min-1mm-No_Insert.m.zip
Instrument Name:Agilent 1260
Column Name:Phenomenex Luna NH2 (150 x 1mm, 3um)
Chromatography Type:HILIC
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