Summary of study ST000016

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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/
InstituteUniversity 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)*.xml
Uploaded File Size21 G
Release Date2013-10-24
Release Version1

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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
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