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.
| Study ID | ST000016 |
| Study Title | NPM-ALK metabolic regulation |
| Study Type | LC-MS analysis (Untargeted) |
| Study Summary | The 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 |
| Department | Dept. of Pathology |
| Laboratory | Lim Lab (MCTP) |
| Last Name | McDonnell |
| First Name | Scott |
| scottmcd@med.umich.edu | |
| Phone | 734-936-1873 |
| Submit Date | 2013-09-24 |
| Num Groups | 23 |
| Total Subjects | 110 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Uploaded File Size | 21 G |
| Analysis Type Detail | LC-MS |
| Release Date | 2013-10-24 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
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 |
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 |
