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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
Study ID | ST000159 |
Study Title | U13C-Glutamine and U13C-Glucose Flux Analysis (MFA SiHa B16F10) |
Study Type | 13C mass isotopomer analysis (LCMS flux studies) |
Study Summary | Oxygenated 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 |
Department | Biomedical Research Core Facilities |
Laboratory | Metabolomics core |
Last Name | Kachman |
First Name | Maureen |
Address | 6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714 |
mkachman@umich.edu | |
Submit Date | 2014-12-02 |
Num Groups | 6 |
Total Subjects | 30 |
Raw Data Available | Yes |
Raw Data File Type(s) | d |
Uploaded File Size | 1.1 G |
Analysis Type Detail | LC-MS |
Release Date | 2015-04-28 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
Project ID: | PR000138 |
Project DOI: | doi: 10.21228/M84G67 |
Project Title: | SiHa B16F10 |
Project Summary: | U13C-Glutamine and U13C-Glucose Flux Analysis |
Institute: | University Catholic of Louvain (UCL) Medical School |
Department: | Pharmacology |
Laboratory: | Sonveaux Lab |
Last Name: | Sonveaux |
First Name: | Pierre |
Address: | Belgium |
Email: | pierre.sonveaux@uclouvain.be |
Phone: | 32 2 764 52 67 |
Subject:
Subject ID: | SU000178 |
Subject Type: | Human |
Subject Species: | Homo sapiens |
Taxonomy ID: | 9606 |
Species Group: | Mammals |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
mb_sample_id | local_sample_id | Condition | Labeling |
---|---|---|---|
SA008547 | S00016847 | Control group 1 | U13CGlutamine |
SA008548 | S00016850 | Control group 1 | U13CGlutamine |
SA008549 | S00016851 | Control group 1 | U13CGlutamine |
SA008550 | S00016849 | Control group 1 | U13CGlutamine |
SA008551 | S00016848 | Control group 1 | U13CGlutamine |
SA008552 | S00016858 | Control line group 2 | U13CGlucose |
SA008553 | S00016859 | Control line group 2 | U13CGlucose |
SA008554 | S00016860 | Control line group 2 | U13CGlucose |
SA008555 | S00016857 | Control line group 2 | U13CGlucose |
SA008556 | S00016861 | Control line group 2 | U13CGlucose |
SA008557 | S00016867 | Control line group 3 | U13CGlucose |
SA008558 | S00016868 | Control line group 3 | U13CGlucose |
SA008559 | S00016869 | Control line group 3 | U13CGlucose |
SA008560 | S00016871 | Control line group 3 | U13CGlucose |
SA008561 | S00016870 | Control line group 3 | U13CGlucose |
SA008562 | S00016865 | Selected line group 2 | U13CGlucose |
SA008563 | S00016864 | Selected line group 2 | U13CGlucose |
SA008564 | S00016866 | Selected line group 2 | U13CGlucose |
SA008565 | S00016863 | Selected line group 2 | U13CGlucose |
SA008566 | S00016862 | Selected line group 2 | U13CGlucose |
SA008567 | S00016873 | Selected line group 3 | U13CGlucose |
SA008568 | S00016874 | Selected line group 3 | U13CGlucose |
SA008569 | S00016875 | Selected line group 3 | U13CGlucose |
SA008570 | S00016876 | Selected line group 3 | U13CGlucose |
SA008571 | S00016872 | Selected line group 3 | U13CGlucose |
SA008572 | S00016854 | Treated group 1 | U13CGlutamine |
SA008573 | S00016856 | Treated group 1 | U13CGlutamine |
SA008574 | S00016852 | Treated group 1 | U13CGlutamine |
SA008575 | S00016853 | Treated group 1 | U13CGlutamine |
SA008576 | S00016855 | Treated group 1 | U13CGlutamine |
Showing results 1 to 30 of 30 |
Collection:
Collection ID: | CO000164 |
Collection Summary: | - |
Sample Type: | Cell Line |
Treatment:
Treatment ID: | TR000184 |
Sample Preparation:
Sampleprep ID: | SP000178 |
Sampleprep Summary: | - |
Sampleprep Protocol Filename: | Fluxomics_analysis_protocol-2015-03-11.docx |
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 |
MS:
MS ID: | MS000201 |
Analysis ID: | AN000251 |
Instrument Name: | Agilent 6520 QTOF |
Instrument Type: | QTOF |
MS Type: | ESI |
Ion Mode: | NEGATIVE |
Acquisition Parameters File: | QTOF-002-HILIC-35min-1mm.m.zip |
Processing Parameters File: | EX00381-Quant-Flux-Method.m.zip |