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.
| Study ID | ST003060 |
| Study Title | Fluxomics of hormone deprivation in ER+ breast cancer cell lines |
| Study Type | Fluxomics |
| Study Summary | Despite 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 |
| Department | Molecular and Systems Biology |
| Laboratory | Miller |
| Last Name | Miller |
| First Name | Todd |
| Address | Hanover, NH |
| Todd.W.Miller@Dartmouth.edu | |
| Phone | 603-646-5507 |
| Submit Date | 2024-01-15 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-02-14 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001906 |
| Project DOI: | doi: 10.21228/M8BQ6H |
| Project Title: | Investigation of metabolism in ER+ breast cancer |
| Project Type: | MS |
| Project Summary: | This study aims to observe alterations in substrate preference in ER+ breast cancer cell lines when subjected to endocrine therapy |
| Institute: | University of Michigan |
| Department: | MRC2 |
| Laboratory: | BRCF metabolomics core |
| Last Name: | Kachman |
| First Name: | Maureen |
| Address: | Ann Arbor, MI, USA |
| Email: | mkachman@med.umich.edu |
| Phone: | 734-232-0842 |
Subject:
| Subject ID: | SU003175 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | 13C label | Hormone treatment |
|---|---|---|---|
| SA331845 | Blank | Blank | Blank |
| SA331847 | MCF7 HD glucose non-labeled control | glucose | No |
| SA331848 | MCF7 HD glucose_3 | glucose | No |
| SA331849 | MCF7 HD glucose_1 | glucose | No |
| SA331850 | MCF7 HD glucose_2 | glucose | No |
| SA331851 | MCF7 E2 glucose_2 | glucose | Yes |
| SA331852 | MCF7 E2 glucose_1 | glucose | Yes |
| SA331853 | MCF7 E2 glucose_3 | glucose | Yes |
| SA331854 | MCF7 E2 glucose non-labeled control | glucose | Yes |
| SA331855 | MCF7 HD oleic acid non-labeled control | oleic acid | No |
| SA331856 | MCF7 HD oleic acid_1 | oleic acid | No |
| SA331857 | MCF7 HD oleic acid_3 | oleic acid | No |
| SA331858 | MCF7 HD oleic acid_2 | oleic acid | No |
| SA331859 | MCF7 E2 oleic acid_1 | oleic acid | Yes |
| SA331860 | MCF7 E2 oleic acid_2 | oleic acid | Yes |
| SA331861 | MCF7 E2 oleic acid_3 | oleic acid | Yes |
| SA331862 | MCF7 E2 oleic acid non-labeled control | oleic acid | Yes |
| SA331846 | Pool | Pool | Pool |
| Showing results 1 to 18 of 18 |
Collection:
| Collection ID: | CO003168 |
| Collection Summary: | Cells were washed with 150 mM ammonium acetate and flash frozen, before storage at -80deg C. |
| Sample Type: | Breast cancer cells |
Treatment:
| Treatment ID: | TR003184 |
| Treatment Summary: | Cells are hormone deprived for 21 days, before reseeding into 10 cm dishes at 3-5e6 cells/dish. After 2 days of allowing the cells to properly adhere, cells were labeled with 4.5 g/L 13C-glucose or 100 uM 13C-oleic acid according to the sample preparation guidelines. |
Sample Preparation:
| Sampleprep ID: | SP003181 |
| Sampleprep Summary: | Glycolysis-TCA (GlyTCA) by Ion Pairing UPLC-QTOF mass spectrometry |
| Sampleprep Protocol Filename: | GlyTCA_SOP_QTOF-with-prep-V1_20240118.pdf |
Combined analysis:
| Analysis ID | AN005015 |
|---|---|
| Analysis type | MS |
| Chromatography type | Ion pair |
| Chromatography system | Agilent 1290 Infinity II |
| Column | Agilent ZORBAX RRHD Extend-C18 (150 x 2.1mm, 1.8um, 80Å) |
| MS Type | ESI |
| MS instrument type | QTOF |
| MS instrument name | Agilent 6545 QTOF |
| Ion Mode | NEGATIVE |
| Units | counts |
Chromatography:
| Chromatography ID: | CH003788 |
| Chromatography Summary: | Ion Pairing UPLC |
| Instrument Name: | Agilent 1290 Infinity II |
| Column Name: | Agilent ZORBAX RRHD Extend-C18 (150 x 2.1mm, 1.8um, 80Å) |
| Column Temperature: | 35 |
| Flow Gradient: | (Time PercentA PercentB PercentC Flow) (2 100 0 0 0.25) (12 1 99 0 0.25) (19.5 1 99 0 0.25) (20 5 0 95 0.5) (21 5 0 95 0.8) (22 5 0 95 0.8) (26 5 0 95 0.6) (26.1 5 0 95 0.4) (26.2 100 0 0 0.4) (31.8 100 0 0 0.25) (32 100 0 0 0.25) |
| Flow Rate: | 0.25 ml/min |
| Solvent A: | 97% water, 3% methanol, 5mM tributylamine, 5.5mM acetic acid, 12.5nM medronic acid |
| Solvent B: | 100% methanol, 5mM tributylamine, 5.5mM acetic acid, 12.5nM medronic acid |
| Chromatography Type: | Ion pair |
| Solvent C: | 100% Acetonitrile |
MS:
| MS ID: | MS004754 |
| Analysis ID: | AN005015 |
| Instrument Name: | Agilent 6545 QTOF |
| Instrument Type: | QTOF |
| MS Type: | ESI |
| MS Comments: | All data acquisition and processing done using vendor software (Agilent) |
| Ion Mode: | NEGATIVE |
| Acquisition Parameters File: | M001_30min_profile_MS1_10ul_WBsensON_AcqMethodReport.pdf |
