Summary of Study ST002863

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 PR001786. The data can be accessed directly via it's Project DOI: 10.21228/M8VB1G This work is supported by NIH grant, U2C- DK119886.

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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 IDST002863
Study TitleMetabolic profiling and glucose tracing in naive and Enzalutamide-treated 16D prostate cancer cells
Study SummaryAdvanced prostate cancers are treated with therapies targeting the androgen receptor (AR) signaling pathway. While many tumors initially respond to AR inhibition, nearly all develop resistance. It is critical to understand how prostate tumor cells respond to AR inhibition in order to exploit therapy-induced phenotypes prior to the outgrowth of treatment-resistant disease. Here, we comprehensively characterize the effect of AR blockade on prostate cancer metabolism using transcriptomics, metabolomics and bioenergetics approaches. The metabolic response to AR inhibition is defined by reduced glycolysis, robust elongation of mitochondria, and increased reliance on mitochondrial oxidative metabolism. We establish DRP1 activity and MYC signaling as mediators of AR blockade-induced metabolic phenotypes. Rescuing DRP1 phosphorylation after AR inhibition restores mitochondrial fission, while rescuing MYC restores glycolytic activity and prevents sensitivity to complex I inhibition. Our study provides new insight into the regulation of treatment-induced metabolic phenotypes and vulnerabilities in prostate cancer. In the MS data, M0, M1, M2, M3,... represent isotopologues of each metabolite.
Institute
University of California, Los Angeles
DepartmentMolecular, Cell and Developmental Biology
LaboratoryAndrew Goldstein
Last NameGoldstein
First NameAndrew
Address610 Charles E Young Dr East, Goldstein Lab 3141 Terasaki Life Sci Bld, Los Angeles, CA, 90095, USA
EmailAGoldstein@mednet.ucla.edu
Phone3102061402
Submit Date2023-09-11
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2023-09-19
Release Version1
Andrew Goldstein Andrew Goldstein
https://dx.doi.org/10.21228/M8VB1G
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN004695
Analysis type MS
Chromatography type HILIC
Chromatography system Thermo Vanquish
Column Phenomenex Luna NH2 (150 x 2mm,3um)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive Orbitrap
Ion Mode UNSPECIFIED
Units Abundance

Chromatography:

Chromatography ID:CH003535
Chromatography Summary:Dried metabolites were resuspended in 50% ACN:water and 1/10th was loaded onto a Luna 3um NH2 100A (150 × 2.0 mm) column (Phenomenex). The chromatographic separation was performed on a Vanquish Flex (Thermo Fisher Scientific) with mobile phases A (5 mM NH4AcO pH 9.9) and B (ACN) and a flow rate of 200 μl/minute. A linear gradient from 15% A to 95% A over 18 minutes was followed by 9 minutes isocratic flow at 95% A and reequilibration to 15% A.
Instrument Name:Thermo Vanquish
Column Name:Phenomenex Luna NH2 (150 x 2mm,3um)
Column Temperature:35
Flow Gradient:Linear gradient was as follows: 15% A to 95% A over 18 minutes was followed by 9 minutes isocratic flow at 95% A and reequilibration to 15% A
Flow Rate:200 ul/minute
Solvent A:5 mM NH4AcO pH 9.9
Solvent B:ACN
Chromatography Type:HILIC
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