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 |
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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. |
