PXD048700
PXD048700 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Mitochondrial respiration is a targetable vulnerability of endocrine persistence in ER+ breast cancer |
| Description | 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. |
| HostingRepository | MassIVE |
| AnnounceDate | 2024-12-23 |
| AnnouncementXML | Submission_2024-12-23_11:18:53.200.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Mark Adamo |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Carbamidomethyl; Oxidation; TMT6plex |
| Instrument | Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-01-18 14:08:04 | ID requested | |
| ⏵ 1 | 2024-12-23 11:18:53 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: ER+, breast cancer, mitochondrial respiration, glycolysis, oxidative phosphorylation, fulvestrant, endocrine therapy |
Contact List
| Arminja Kettenbach | |
|---|---|
| contact affiliation | The Geisel School of Medicine at Dartmouth |
| contact email | arminja.n.kettenbach@dartmouth.edu |
| lab head | |
| Mark Adamo | |
| contact affiliation | Dartmouth College |
| contact email | mark.e.adamo@dartmouth.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/v06/MSV000093890/ |
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