Summary of Study ST003060

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 PR001906. The data can be accessed directly via it's Project DOI: 10.21228/M8BQ6H 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 IDST003060
Study TitleFluxomics of hormone deprivation in ER+ breast cancer cell lines
Study TypeFluxomics
Study SummaryDespite adjuvant treatment with endocrine therapies, estrogen receptor-positive (ER+) breast cancers recur in a significant proportion of patients. Recurrences are attributable to clinically undetectable endocrine-tolerant persister cancer cells that retain tumor-forming potential. We observed that persistence occurred stochastically without genetic predisposition. Genome-wide screening in persisters revealed a survival mechanism involving metabolic reprogramming with reliance upon mitochondrial respiration. Proteomic profiling showed reduced levels of glycolytic proteins in persisters. Metabolic tracing of glucose revealed an energy-depleted state in persisters where oxidative phosphorylation was required to generate ATP. Persisters exhibiting residual proliferation in human breast tumors following neoadjuvant endocrine therapy showed increased mitochondrial content. Pharmacological inhibition of oxidative phosphorylation suppressed the tumor-forming potential of persisters and synergized with the anti-estrogen fulvestrant to induce regression of patient-derived xenografts, supporting therapeutic targeting of mitochondrial metabolism to help eradicate residual disease.
Institute
Dartmouth College
DepartmentMolecular and Systems Biology
LaboratoryMiller
Last NameMiller
First NameTodd
AddressHanover, NH
EmailTodd.W.Miller@Dartmouth.edu
Phone603-646-5507
Submit Date2024-01-15
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2024-02-14
Release Version1
Todd Miller Todd Miller
https://dx.doi.org/10.21228/M8BQ6H
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

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

mb_sample_id local_sample_id 13C label Hormone treatment
SA331845BlankBlank Blank
SA331847MCF7 HD glucose non-labeled controlglucose No
SA331848MCF7 HD glucose_3glucose No
SA331849MCF7 HD glucose_1glucose No
SA331850MCF7 HD glucose_2glucose No
SA331851MCF7 E2 glucose_2glucose Yes
SA331852MCF7 E2 glucose_1glucose Yes
SA331853MCF7 E2 glucose_3glucose Yes
SA331854MCF7 E2 glucose non-labeled controlglucose Yes
SA331855MCF7 HD oleic acid non-labeled controloleic acid No
SA331856MCF7 HD oleic acid_1oleic acid No
SA331857MCF7 HD oleic acid_3oleic acid No
SA331858MCF7 HD oleic acid_2oleic acid No
SA331859MCF7 E2 oleic acid_1oleic acid Yes
SA331860MCF7 E2 oleic acid_2oleic acid Yes
SA331861MCF7 E2 oleic acid_3oleic acid Yes
SA331862MCF7 E2 oleic acid non-labeled controloleic acid Yes
SA331846PoolPool Pool
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