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PXD041545

PXD041545 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlemTOR Inhibition Suppresses Salinomycin-Induced Ferroptosis in Breast Cancer Stem Cells by Ironing Out Mitochondrial Dysfunctions
DescriptionFerroptosis 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:18:14.823.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChiara guerrera
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-04-14 08:43:43ID requested
12023-12-20 09:24:51announced
22024-10-22 06:18:15announced2024-10-22: 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 affiliationPlatform Proteomic Necker Faculty of Medecine, University Paris Cité SFR Necker INSERM US24
contact emailchiara.guerrera@inserm.fr
lab head
Chiara guerrera
contact affiliationNecker proteomics, INSERM
contact emailchiara.guerrera@inserm.fr
dataset submitter
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Dataset FTP location
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