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.
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 | ST002863 |
Study Title | Metabolic profiling and glucose tracing in naive and Enzalutamide-treated 16D prostate cancer cells |
Study Summary | Advanced 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 |
Department | Molecular, Cell and Developmental Biology |
Laboratory | Andrew Goldstein |
Last Name | Goldstein |
First Name | Andrew |
Address | 610 Charles E Young Dr East, Goldstein Lab 3141 Terasaki Life Sci Bld, Los Angeles, CA, 90095, USA |
AGoldstein@mednet.ucla.edu | |
Phone | 3102061402 |
Submit Date | 2023-09-11 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Thermo) |
Analysis Type Detail | LC-MS |
Release Date | 2023-09-19 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
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 |