PXD058009

PXD058009 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Phosphoproteomics landscape of lung DTP
Description	Osimertinib is the first-line therapy for EGFR-mutated non-small cell lung cancer, but acquired resistance commonly develops, linked to a drug-tolerant persister (DTP) cell state that promotes survival and eventual resistance. Using data-independent acquisition mass spectrometry (DIA-MS), we mapped dynamic proteomic and phosphoproteomic changes in DTPs. While osimertinib initially blocks EGFR signaling, DTPs show activation in ribosome synthesis and protein translation pathways, with resistance emerging via EGFR reactivation and anti-apoptotic mechanisms, including YAP1 and mTOR-BAD hyperphosphorylation. Elevated phosphorylation of CDK1 substrates in DTPs was observed, and inhibiting CDK1-mediated SAMHD1 activation impaired DTP growth. This study highlights key DTP mechanisms, suggesting biomarkers and therapeutic targets to delay resistance.
HostingRepository	PRIDE
AnnounceDate	2025-11-10
AnnouncementXML	Submission_2025-11-10_08:19:21.156.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hsiang-En Hsu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-18 13:57:22	ID requested
⏵ 1	2025-11-10 08:19:22	announced

Publication List

10.1038/s44320-025-00141-1;
Hsu HE, Martin MJ, Weng SH, Kitata RB, Nagelli S, Chang CY, Hess S, Chen YJ, Phosphoproteomics of osimertinib-tolerant persister cells reveals targetable kinase-substrate signatures. Mol Syst Biol, 21(11):1547-1562(2025) [pubmed]

10.1038/s44320-025-00141-1;

Hsu HE, Martin MJ, Weng SH, Kitata RB, Nagelli S, Chang CY, Hess S, Chen YJ, Phosphoproteomics of osimertinib-tolerant persister cells reveals targetable kinase-substrate signatures. Mol Syst Biol, 21(11):1547-1562(2025) [pubmed]

Keyword List

submitter keyword: LC-MSMS, Lung,Huamn, DTP

submitter keyword: LC-MSMS, Lung,Huamn, DTP

Contact List

Yu-Ju Chen
contact affiliation	Institute of Chemistry, Academia Sinica, Taiwan
contact email	yujuchen@gate.sinica.edu.tw
lab head
Hsiang-En Hsu
contact affiliation	Academia Sinica
contact email	carter700507@gmail.com
dataset submitter

Full Dataset Link List

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/2025/11/PXD058009
PRIDE project 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://ftp.pride.ebi.ac.uk/pride/data/archive/2025/11/PXD058009

PRIDE project URI

Repository Record List

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