PXD041545 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | mTOR Inhibition Suppresses Salinomycin-Induced Ferroptosis in Breast Cancer Stem Cells by Ironing Out Mitochondrial Dysfunctions |
Description | Ferroptosis constitutes a promising therapeutic strategy against cancer by efficiently targeting the highly tumorigenic and treatment-resistant cancer stem cells (CSCs). We previously showed that the lysosomal iron-targeting drug Salinomycin (Sal) was able to eliminate CSCs by triggering ferroptosis. Here, in a well-established breast CSCs model (human mammary epithelial HMLER CD24low/CD44high), we identified that pharmacological inhibition of mechanistic target of rapamycin (mTOR), suppresses Sal-induced ferroptosis. Mechanistically, mTOR inhibition modulates iron cellular flux and prevents the iron and ROS bursts induced by Sal. Besides, integration of multi-omics data identified mitochondria as a key target of Sal action. We demonstrated that mTOR inhibition prevents Sal-induced mitochondrial functional and structural alteration, and that Sal-induced metabolic plasticity is mainly dependent on the mTOR pathway. Overall, our findings provide experimental evidences on the detailed mechanisms of mTOR as a crucial effector of Sal-induced ferroptosis, and gives proof-of-concept that careful evaluation of such combination therapy (here mTOR and ferroptosis co-targeting) is required for effective treatment. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:18:14.823.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Chiara guerrera |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | timsTOF Pro |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-04-14 08:43:43 | ID requested | |
1 | 2023-12-20 09:24:51 | announced | |
⏵ 2 | 2024-10-22 06:18:15 | announced | 2024-10-22: Updated project metadata. |
Publication List
Cosialls E, Pacreau E, Duruel C, Ceccacci S, Elhage R, Desterke C, Roger K, Guerrera C, Ducloux R, Souquere S, Pierron G, Nemazanyy I, Kelly M, Dalmas E, Chang Y, Goffin V, Mehrpour M, Hama, ï A, mTOR inhibition suppresses salinomycin-induced ferroptosis in breast cancer stem cells by ironing out mitochondrial dysfunctions. Cell Death Dis, 14(11):744(2023) [pubmed] |
10.1038/s41419-023-06262-5; |
Keyword List
submitter keyword: mTOR Pathway, Mitochondria, Metabolic Reprogramming |
Breast Cancer Stem Cells,Ferroptosis, Iron Homeostasis |
Contact List
Ida Chiara Guerrera |
contact affiliation | Platform Proteomic Necker Faculty of Medecine, University Paris Cité SFR Necker INSERM US24 |
contact email | chiara.guerrera@inserm.fr |
lab head | |
Chiara guerrera |
contact affiliation | Necker proteomics, INSERM |
contact email | chiara.guerrera@inserm.fr |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD041545
- Label: PRIDE project
- Name: mTOR Inhibition Suppresses Salinomycin-Induced Ferroptosis in Breast Cancer Stem Cells by Ironing Out Mitochondrial Dysfunctions