PXD041545

PXD041545 is an original dataset announced via ProteomeXchange.

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

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.

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;

submitter keyword: mTOR Pathway, Mitochondria, Metabolic Reprogramming

Breast Cancer Stem Cells,Ferroptosis, Iron Homeostasis

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

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://ftp.pride.ebi.ac.uk/pride/data/archive/2023/12/PXD041545

PRIDE project URI

• PRIDE
  1. PXD041545
     1. Label: PRIDE project
     2. Name: mTOR Inhibition Suppresses Salinomycin-Induced Ferroptosis in Breast Cancer Stem Cells by Ironing Out Mitochondrial Dysfunctions