Summary of Study ST001730

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 PR001108. The data can be accessed directly via it's Project DOI: 10.21228/M8GM5B 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.

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Study IDST001730
Study TitleMitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer chemoresistance
Study SummaryChemotherapy remains the standard of care for most cancers worldwide, however development of chemoresistance due to the presence of the drug-effluxing ABC transporters remains a significant problem. The development of safe and effective means to overcome chemoresistance is critical for achieving durable remissions in many cancer patients. We have investigated the energetic demands of ABC transporters in the context of the metabolic adaptations of chemoresistant cancer cells. Here we show that ABC transporters use mitochondrial-derived ATP as a source of energy to efflux drugs out of cancer cells. We further demonstrate that the loss of MCJ (DnaJC15), an endogenous negative regulator of mitochondrial respiration, in chemoresistant cancer cells boosts their ability to produce ATP from mitochondria and fuel ABC transporters. We have developed novel MCJ mimetics that can attenuate mitochondrial respiration and safely overcome chemoresistance in vitro and in vivo. Administration of MCJ mimetics in combination with standard chemotherapeutic drugs could therefore become an new strategy for treatment of multiple cancers.
Institute
University of Colorado Denver
DepartmentBiochemistry and Molecular Genetics
LaboratoryAngelo D'Alessandro
Last NameCulp-Hill
First NameRachel
Address12801 E 17th Ave L18-9403D, Aurora, Colorado, 80045, USA
Emailrachel.hill@cuanschutz.edu
Phone303-724-5798
Submit Date2021-03-17
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2021-03-31
Release Version1
Rachel Culp-Hill Rachel Culp-Hill
https://dx.doi.org/10.21228/M8GM5B
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id line
SA162621nci-adr-res-1NCI-ADR-RES
SA162622nci-adr-res-4NCI-ADR-RES
SA162623nci-adr-res-3NCI-ADR-RES
SA162624nci-adr-res-2NCI-ADR-RES
SA162625ovcar8-4OVCAR8
SA162626ovcar8-1OVCAR8
SA162627ovcar8-2OVCAR8
SA162628ovcar8-3OVCAR8
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