Summary of Study ST000016

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 PR000015. The data can be accessed directly via it's Project DOI: 10.21228/M8BC7F This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST000016
Study TitleNPM-ALK metabolic regulation
Study TypeLC-MS analysis (Untargeted)
Study SummaryThe mechanisms underlying the pathogenesis of the constitutively active tyrosine kinase nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) expressing anaplastic large cell lymphoma are not completely understood. Here we show using an integrated phosphoproteomic and metabolomic strategy that NPM-ALK induces a metabolic shift toward aerobic glycolysis, increased lactate production, and biomass production. The metabolic shift is mediated through the anaplastic lymphoma kinase (ALK) phosphorylation of the tumor-specific isoform of pyruvate kinase (PKM2) at Y105, resulting in decreased enzymatic activity. Small molecule activation of PKM2 or expression of Y105F PKM2 mutant leads to reversal of the metabolic switch with increased oxidative phosphorylation and reduced lactate production coincident with increased cell death, decreased colony formation, and reduced tumor growth in an in vivo xenograft model. This study provides comprehensive profiling of the phosphoproteomic and metabolomic consequences of NPM-ALK expression and reveals a novel role of ALK in the regulation of multiple components of cellular metabolism. Our studies show that PKM2 is a novel substrate of ALK and plays a critical role in mediating the metabolic shift toward biomass production and tumorigenesis. Research is published: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739039/
Institute
University of Michigan
DepartmentDept. of Pathology
LaboratoryLim Lab (MCTP)
Last NameMcDonnell
First NameScott
Emailscottmcd@med.umich.edu
Phone734-936-1873
Submit Date2013-09-24
Num Groups23
Total Subjects110
Raw Data AvailableYes
Raw Data File Type(s)mzML
Uploaded File Size21 G
Analysis Type DetailLC-MS
Release Date2013-10-24
Release Version1
Scott McDonnell Scott McDonnell
https://dx.doi.org/10.21228/M8BC7F
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000015
Project DOI:doi: 10.21228/M8BC7F
Project Title:NPM-ALK
Project Type:MS study
Project Summary:Determination of global metabolic changes induced by NPM-ALK
Institute:University of Michigan
Department:Dept. of Pathology
Laboratory:Megan Lim
Last Name:Lim
First Name:Megan
Address:University Michigan, 2900 Huron Parkway, Ann Arbor, MI 48105
Email:meganlim@umich.edu
Phone:734-936-1873
Funding Source:CA140806-01;DE119249;CA136905

Subject:

Subject ID:SU000032
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 Cell type Material Treatment
SA001009S00004486293T Cells K210R NPM-ALK tf
SA001010S00004485293T Cells K210R NPM-ALK tf
SA001011S00004487293T Cells K210R NPM-ALK tf
SA001012S00004488293T Cells K210R NPM-ALK tf
SA001013S00004489293T Cells K210R NPM-ALK tf
SA001019S00004477293T Cells No transfection
SA001020S00004479293T Cells No transfection
SA001021S00004478293T Cells No transfection
SA001022S00004476293T Cells No transfection
SA001023S00004475293T Cells No transfection
SA001029S00004481293T Cells WT NPM-ALK tf
SA001030S00004482293T Cells WT NPM-ALK tf
SA001031S00004483293T Cells WT NPM-ALK tf
SA001032S00004484293T Cells WT NPM-ALK tf
SA001033S00004480293T Cells WT NPM-ALK tf
SA001014S00004543293T Media K210R NPM-ALK tf
SA001015S00004540293T Media K210R NPM-ALK tf
SA001016S00004541293T Media K210R NPM-ALK tf
SA001017S00004542293T Media K210R NPM-ALK tf
SA001018S00004544293T Media K210R NPM-ALK tf
SA001024S00004534293T Media No transfection
SA001025S00004531293T Media No transfection
SA001026S00004530293T Media No transfection
SA001027S00004533293T Media No transfection
SA001028S00004532293T Media No transfection
SA001034S00004538293T Media WT NPM-ALK tf
SA001035S00004536293T Media WT NPM-ALK tf
SA001036S00004539293T Media WT NPM-ALK tf
SA001037S00004537293T Media WT NPM-ALK tf
SA001038S00004535293T Media WT NPM-ALK tf
SA000929S00004505DEL Cells CEP-26939
SA000930S00004508DEL Cells CEP-26939
SA000931S00004507DEL Cells CEP-26939
SA000932S00004506DEL Cells CEP-26939
SA000933S00004509DEL Cells CEP-26939
SA000968S00004502DEL Cells DMSO
SA000969S00004500DEL Cells DMSO
SA000970S00004501DEL Cells DMSO
SA000971S00004504DEL Cells DMSO
SA000972S00004503DEL Cells DMSO
SA000948S00004560DEL Media CEP-26939
SA000949S00004561DEL Media CEP-26939
SA000950S00004563DEL Media CEP-26939
SA000951S00004564DEL Media CEP-26939
SA000952S00004562DEL Media CEP-26939
SA000989S00004557DEL Media DMSO
SA000990S00004559DEL Media DMSO
SA000991S00004558DEL Media DMSO
SA000992S00004556DEL Media DMSO
SA000993S00004555DEL Media DMSO
SA000934S00004525SR786 Cells CEP-26939
SA000935S00004528SR786 Cells CEP-26939
SA000936S00004527SR786 Cells CEP-26939
SA000937S00004526SR786 Cells CEP-26939
SA000938S00004529SR786 Cells CEP-26939
SA000973S00004523SR786 Cells DMSO
SA000974S00004522SR786 Cells DMSO
SA000975S00004524SR786 Cells DMSO
SA000976S00004521SR786 Cells DMSO
SA000977S00004520SR786 Cells DMSO
SA000953S00004584SR786 Media CEP-26939
SA000954S00004583SR786 Media CEP-26939
SA000955S00004582SR786 Media CEP-26939
SA000956S00004581SR786 Media CEP-26939
SA000957S00004580SR786 Media CEP-26939
SA000994S00004576SR786 Media DMSO
SA000995S00004578SR786 Media DMSO
SA000996S00004575SR786 Media DMSO
SA000997S00004577SR786 Media DMSO
SA000998S00004579SR786 Media DMSO
SA000939S00004497SUDHL-1 Cells CEP-26939
SA000940S00004498SUDHL-1 Cells CEP-26939
SA000941S00004496SUDHL-1 Cells CEP-26939
SA000942S00004499SUDHL-1 Cells CEP-26939
SA000978S00004495SUDHL-1 Cells CEP-26939
SA000979S00004490SUDHL-1 Cells DMSO
SA000980S00004494SUDHL-1 Cells DMSO
SA000981S00004491SUDHL-1 Cells DMSO
SA000982S00004492SUDHL-1 Cells DMSO
SA000983S00004493SUDHL-1 Cells DMSO
SA000958S00004554SUDHL-1 Media CEP-26939
SA000959S00004551SUDHL-1 Media CEP-26939
SA000960S00004552SUDHL-1 Media CEP-26939
SA000961S00004550SUDHL-1 Media CEP-26939
SA000962S00004553SUDHL-1 Media CEP-26939
SA000999S00004549SUDHL-1 Media DMSO
SA001000S00004548SUDHL-1 Media DMSO
SA001001S00004546SUDHL-1 Media DMSO
SA001002S00004547SUDHL-1 Media DMSO
SA001003S00004545SUDHL-1 Media DMSO
SA000943S00004517SUPM2 Cells CEP-26939
SA000944S00004516SUPM2 Cells CEP-26939
SA000945S00004515SUPM2 Cells CEP-26939
SA000946S00004519SUPM2 Cells CEP-26939
SA000947S00004518SUPM2 Cells CEP-26939
SA000984S00004512SUPM2 Cells DMSO
SA000985S00004510SUPM2 Cells DMSO
SA000986S00004513SUPM2 Cells DMSO
SA000987S00004511SUPM2 Cells DMSO
SA000988S00004514SUPM2 Cells DMSO
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Collection:

Collection ID:CO000016
Collection Summary:-
Sample Type:Lymphoma cells

Treatment:

Treatment ID:TR000030
Treatment Compound:No transfection | WT NPM-ALK tf | K210R NPM-ALK tf | DMSO | CEP-26939

Sample Preparation:

Sampleprep ID:SP000029
Sampleprep Summary:-
Sampleprep Protocol Filename:EX00125-Sample_preparation_protocol.pdf

Combined analysis:

Analysis ID AN000033
Analysis type MS
Chromatography type Reversed phase
Chromatography system Agilent 1200
Column Waters Acquity HSS T3 reversed-phase
MS Type ESI
MS instrument type QTOF
MS instrument name Agilent 6530 QTOF
Ion Mode POSITIVE
Units Peak area

Chromatography:

Chromatography ID:CH000016
Methods ID:EX00125-LCMS-method.pdf
Instrument Name:Agilent 1200
Column Name:Waters Acquity HSS T3 reversed-phase
Column Temperature:40C
Flow Gradient:0-0.5 min 1% B, 0.5-2 min 1-99% B, 2-6 min 99% B, 6-9 min 1% B.
Flow Rate:0.35 mL/min
Solvent A:100% water; 0.1% formic acid
Solvent B:100% methanol; 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS000032
Analysis ID:AN000033
Instrument Name:Agilent 6530 QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:POSITIVE
Acquisition Parameters File:EX00125-LCMS-method.pdf
Processing Parameters File:EX00125-Data_analysis-method.pdf
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