Summary of Study ST002852
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 | ST002852 |
| Study Title | MYC is a regulator of androgen receptor inhibition-induced metabolic requirements in prostate cancer |
| 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. |
| Institute | University of California, Los Angeles |
| Department | Biological Chemistry |
| Laboratory | Heather Christofk |
| Last Name | Matulionis |
| First Name | Nedas |
| Address | 615 Charles E Young Dr S, BSRB 354-05 |
| nmatulionis@mednet.ucla.edu | |
| Phone | 3102060163 |
| Submit Date | 2023-09-07 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-09-11 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004672 | AN004673 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | HILIC | HILIC |
| Chromatography system | Thermo Vanquish | Thermo Vanquish |
| Column | SeQuant ZIC- pHILIC (150 x 2.1mm,5um) | SeQuant ZIC- pHILIC (150 x 2.1mm,5um) |
| MS Type | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | Peak Area | Peak Area |
Chromatography:
| Chromatography ID: | CH003516 |
| Chromatography Summary: | Samples were run on a Vanquish (Thermo Fisher Scientific) UHPLC system with mobile phase A (20mM ammonium carbonate, pH 9.7) and mobile phase B (100% ACN) at a flow rate of 150 µL/min on a SeQuant ZIC-pHILIC Polymeric column (2.1 × 150 mm 5 μm, EMD Millipore) at 35°C. Separation was achieved with a linear gradient from 20% A to 80% A in 20 minutes followed by a linear gradient from 80% A to 20% A from 20 minutes to 20.5 minutes. 20% A was then held from 20.5 minutes to 28 minutes. |
| Instrument Name: | Thermo Vanquish |
| Column Name: | SeQuant ZIC- pHILIC (150 x 2.1mm,5um) |
| Column Temperature: | 35°C |
| Flow Gradient: | Linear gradient was as follows: 20%A to 80%A (0-20 min), 80%A to 20%A (20-20.5 min), hold 20%A (20.5-28.0 min). |
| Flow Rate: | 150 µL/min |
| Solvent A: | 20 mM Ammonium carbonate, pH 9.7 |
| Solvent B: | 100% Acetonitrile |
| Chromatography Type: | HILIC |
