{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST002859","ANALYSIS_ID":"AN004689","VERSION":"1","CREATED_ON":"September 13, 2023, 3:30 pm"},

"PROJECT":{"PROJECT_TITLE":"MYC is a regulator of AR inhibition-induced metabolic requirements in prostate cancer","PROJECT_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":"UCLA","LABORATORY":"Goldstein Lab","LAST_NAME":"Giafaglione","FIRST_NAME":"Jenna","ADDRESS":"610 Charles E Young Dr S, Los Angeles, CA, 90024, USA","EMAIL":"jgiafaglione@g.ucla.edu","PHONE":"408-728-3065"},

"STUDY":{"STUDY_TITLE":"Glucose tracing in vehicle- and Enzalutamide-treated 16D prostate cancer cells","STUDY_SUMMARY":"In this study, we sought to determine how Enzalutamide treatment alters metabolism in 16D prostate cancer cells.","INSTITUTE":"UCLA","LABORATORY":"Goldstein Lab","LAST_NAME":"Giafaglione","FIRST_NAME":"Jenna","ADDRESS":"610 Charles E Young Dr S, Los Angeles, CA, 90024, USA","EMAIL":"jgiafaglione@g.ucla.edu","PHONE":"408-728-3065"},

"SUBJECT":{"SUBJECT_TYPE":"Cultured cells","SUBJECT_SPECIES":"Homo sapiens","TAXONOMY_ID":"9606"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"Naive-1",
"Factors":{"Treatment":"Vehicle (DMSO)"},
"Additional sample data":{"RAW_FILE_NAME":"Naive-1.D"}
},
{
"Subject ID":"-",
"Sample ID":"Naive-2",
"Factors":{"Treatment":"Vehicle (DMSO)"},
"Additional sample data":{"RAW_FILE_NAME":"Naive-2.D"}
},
{
"Subject ID":"-",
"Sample ID":"Naive-3",
"Factors":{"Treatment":"Vehicle (DMSO)"},
"Additional sample data":{"RAW_FILE_NAME":"Naive-3.D"}
},
{
"Subject ID":"-",
"Sample ID":"LTEnza-1",
"Factors":{"Treatment":"10uM Enzalutamide"},
"Additional sample data":{"RAW_FILE_NAME":"LTEnza-1.D"}
},
{
"Subject ID":"-",
"Sample ID":"LTEnza-2",
"Factors":{"Treatment":"10uM Enzalutamide"},
"Additional sample data":{"RAW_FILE_NAME":"LTEnza-2.D"}
},
{
"Subject ID":"-",
"Sample ID":"LTEnza-3",
"Factors":{"Treatment":"10uM Enzalutamide"},
"Additional sample data":{"RAW_FILE_NAME":"LTEnza-3.D"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"16D prostate cancer cells were cultured with vehicle or Enzalutamide for >2 months.","SAMPLE_TYPE":"Cultured cells"},

"TREATMENT":{"TREATMENT_SUMMARY":"Vehicle- and Enzalutamide-treated 16D cells were cultured in U13C-glucose containing media for 24 hours."},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Cell plates were placed on ice and quickly washed with ice-cold 0.9% (w/v) NaCl. Cells were immediately treated with 500 μL of ice-cold MeOH and 200 μL water containing 1 μg of the internal standard norvaline. Cells were then scraped and placed in 1.5 mL centrifuge tubes kept on ice. Next, 500 μL of chloroform was added, after which samples were vortexed for 1 minute and then spun at 10,000g for 5 minutes at 4C. The aqueous layer was transferred to a GC/MS sample vial and dried overnight using a refrigerated CentriVap."},

"CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"GC","INSTRUMENT_NAME":"Agilent 7890A","COLUMN_NAME":"Agilent DB5-MS (30m x 0.25mm, 0.25um)","SOLVENT_A":"N/A (GC-MS)","SOLVENT_B":"N/A (GC-MS)","FLOW_GRADIENT":"N/A (GC-MS)","FLOW_RATE":"1 ml/min","COLUMN_TEMPERATURE":"320"},

"ANALYSIS":{"ANALYSIS_TYPE":"MS"},

"MS":{"INSTRUMENT_NAME":"Agilent 5977B","INSTRUMENT_TYPE":"GC-TOF","MS_TYPE":"EI","ION_MODE":"POSITIVE","MS_COMMENTS":"Data was analyzed using Agilent MassHunter software. Stable isotope tracing data was corrected for natural abundance of heavy isotopes with FluxFix software using a reference set of unlabeled metabolite standards2."},

"MS_METABOLITE_DATA":{
"Units":"abundance",

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"Metabolites":[{"metabolite_name":"a-Ketoglutarate(M0)"},{"metabolite_name":"a-Ketoglutarate(M1)"},{"metabolite_name":"a-Ketoglutarate(M2)"},{"metabolite_name":"a-Ketoglutarate(M3)"},{"metabolite_name":"a-Ketoglutarate(M4)"},{"metabolite_name":"a-Ketoglutarate(M5)"},{"metabolite_name":"a-Ketoglutarate(M6)"},{"metabolite_name":"Alanine260(M0)"},{"metabolite_name":"Alanine260(M1)"},{"metabolite_name":"Alanine260(M2)"},{"metabolite_name":"Alanine260(M3)"},{"metabolite_name":"Alanine260(M4)"},{"metabolite_name":"Asparagine(M0)"},{"metabolite_name":"Asparagine(M1)"},{"metabolite_name":"Asparagine(M2)"},{"metabolite_name":"Asparagine(M3)"},{"metabolite_name":"Asparagine(M4)"},{"metabolite_name":"Asparagine(M5)"},{"metabolite_name":"Aspartate418(M0)"},{"metabolite_name":"Aspartate418(M1)"},{"metabolite_name":"Aspartate418(M2)"},{"metabolite_name":"Aspartate418(M3)"},{"metabolite_name":"Aspartate418(M4)"},{"metabolite_name":"Aspartate418(M5)"},{"metabolite_name":"Citrate459(M0)"},{"metabolite_name":"Citrate459(M1)"},{"metabolite_name":"Citrate459(M2)"},{"metabolite_name":"Citrate459(M3)"},{"metabolite_name":"Citrate459(M4)"},{"metabolite_name":"Citrate459(M5)"},{"metabolite_name":"Citrate459(M6)"},{"metabolite_name":"Citrate459(M7)"},{"metabolite_name":"Citrate591(M0)"},{"metabolite_name":"Citrate591(M1)"},{"metabolite_name":"Citrate591(M2)"},{"metabolite_name":"Citrate591(M3)"},{"metabolite_name":"Citrate591(M4)"},{"metabolite_name":"Citrate591(M5)"},{"metabolite_name":"Citrate591(M6)"},{"metabolite_name":"Citrate591(M7)"},{"metabolite_name":"Cysteine(M0)"},{"metabolite_name":"Cysteine(M1)"},{"metabolite_name":"Cysteine(M2)"},{"metabolite_name":"Cysteine(M3)"},{"metabolite_name":"Cysteine(M4)"},{"metabolite_name":"Fumarate(M0)"},{"metabolite_name":"Fumarate(M1)"},{"metabolite_name":"Fumarate(M2)"},{"metabolite_name":"Fumarate(M3)"},{"metabolite_name":"Fumarate(M4)"},{"metabolite_name":"Fumarate(M5)"},{"metabolite_name":"GABA(M0)"},{"metabolite_name":"GABA(M1)"},{"metabolite_name":"GABA(M2)"},{"metabolite_name":"GABA(M3)"},{"metabolite_name":"GABA(M4)"},{"metabolite_name":"GABA(M5)"},{"metabolite_name":"Glutamate432(M0)"},{"metabolite_name":"Glutamate432(M1)"},{"metabolite_name":"Glutamate432(M2)"},{"metabolite_name":"Glutamate432(M3)"},{"metabolite_name":"Glutamate432(M4)"},{"metabolite_name":"Glutamate432(M5)"},{"metabolite_name":"Glutamate432(M6)"},{"metabolite_name":"Isoleu-274(M0)"},{"metabolite_name":"Isoleucine274(M0)"},{"metabolite_name":"Isoleucine274(M1)"},{"metabolite_name":"Isoleucine274(M2)"},{"metabolite_name":"Isoleucine274(M3)"},{"metabolite_name":"Isoleucine274(M4)"},{"metabolite_name":"Isoleucine274(M5)"},{"metabolite_name":"Isoleucine274(M6)"},{"metabolite_name":"Isoleucine274(M7)"},{"metabolite_name":"Itaconate(M0)"},{"metabolite_name":"Itaconate(M1)"},{"metabolite_name":"Itaconate(M2)"},{"metabolite_name":"Itaconate(M3)"},{"metabolite_name":"Itaconate(M4)"},{"metabolite_name":"Itaconate(M5)"},{"metabolite_name":"Itaconate(M6)"},{"metabolite_name":"KIC(M0)"},{"metabolite_name":"KIV(M0)"},{"metabolite_name":"KMV(M0)"},{"metabolite_name":"Lactate261(M0)"},{"metabolite_name":"Lactate261(M1)"},{"metabolite_name":"Lactate261(M2)"},{"metabolite_name":"Lactate261(M3)"},{"metabolite_name":"Lactate262(M4)"},{"metabolite_name":"Malate(M0)"},{"metabolite_name":"Malate(M1)"},{"metabolite_name":"Malate(M2)"},{"metabolite_name":"Malate(M3)"},{"metabolite_name":"Malate(M4)"},{"metabolite_name":"Malate(M5)"},{"metabolite_name":"Methionine320(M0)"},{"metabolite_name":"Methionine320(M1)"},{"metabolite_name":"Methionine320(M2)"},{"metabolite_name":"Methionine320(M3)"},{"metabolite_name":"Methionine320(M4)"},{"metabolite_name":"Methionine320(M5)"},{"metabolite_name":"Methionine320(M6)"},{"metabolite_name":"N-AcetylAspartate(M0)"},{"metabolite_name":"N-AcetylAspartate(M1)"},{"metabolite_name":"N-AcetylAspartate(M2)"},{"metabolite_name":"N-AcetylAspartate(M3)"},{"metabolite_name":"N-AcetylAspartate(M4)"},{"metabolite_name":"N-AcetylAspartate(M5)"},{"metabolite_name":"Norvaline 260(M0)"},{"metabolite_name":"Norvaline 260(M1)"},{"metabolite_name":"Norvaline 260(M2)"},{"metabolite_name":"Norvaline 260(M3)"},{"metabolite_name":"Norvaline 288(M0)"},{"metabolite_name":"Norvaline 288(M1)"},{"metabolite_name":"Norvaline 288(M2)"},{"metabolite_name":"Norvaline 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}

}