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
Email	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

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Sample Preparation:

Sampleprep ID:	SP002970
Sampleprep Summary:	After tumor dissection, a maximum of 30mg of tissue was weighed, snap frozen, and stored at -80C until metabolite extraction. To extract metabolites, weighed tumor tissue was added to a bead tube (Thermo Fisher Scientific) containing 1ml 80% methanol plus 10mM potassium trifluoromethanesulfonate (TMSO) internal standard on ice. Samples were homogenized for 1 minute at max speed on a bead homogenizer (Thermo Fisher Scientific). Bead tubes were spun at 17000g at 4C for 10 minutes. The supernatant was transferred to an Eppendorf tube and spun at 17000g at 4C for 10 minutes. A volume of extraction equivalent to 3mg of tumor tissue was transferred to an ABC vial (Thermo Fisher Scientific). All volumes were normalized to 500 µl with 80% methanol containing TMSO internal standard. 80% MeOH was evaporated from the ABC vials using the EZ-2Elite evaporator (Genevac) and samples were stored at -80°C until analysis. Dried metabolites were reconstituted in 100 µL of a 50% acetonitrile (ACN) 50% dH20 solution. Samples were vortexed and spun down for 10 minutes at 17,000g. 70 µL of the supernatant was then transferred to HPLC glass vials. 10 µL of these metabolite solutions were injected per analysis.

Sampleprep ID:

SP002970

Sampleprep Summary:

After tumor dissection, a maximum of 30mg of tissue was weighed, snap frozen, and stored at -80C until metabolite extraction. To extract metabolites, weighed tumor tissue was added to a bead tube (Thermo Fisher Scientific) containing 1ml 80% methanol plus 10mM potassium trifluoromethanesulfonate (TMSO) internal standard on ice. Samples were homogenized for 1 minute at max speed on a bead homogenizer (Thermo Fisher Scientific). Bead tubes were spun at 17000g at 4C for 10 minutes. The supernatant was transferred to an Eppendorf tube and spun at 17000g at 4C for 10 minutes. A volume of extraction equivalent to 3mg of tumor tissue was transferred to an ABC vial (Thermo Fisher Scientific). All volumes were normalized to 500 µl with 80% methanol containing TMSO internal standard. 80% MeOH was evaporated from the ABC vials using the EZ-2Elite evaporator (Genevac) and samples were stored at -80°C until analysis. Dried metabolites were reconstituted in 100 µL of a 50% acetonitrile (ACN) 50% dH20 solution. Samples were vortexed and spun down for 10 minutes at 17,000g. 70 µL of the supernatant was then transferred to HPLC glass vials. 10 µL of these metabolite solutions were injected per analysis.