PXD026834

PXD026834 is an original dataset announced via ProteomeXchange.

Title	IRS1 phosphorylation determines a heritable probability of cancer cells to persist during EGFR inhibition therapy
Description	Stochastic transition of cancer cells between drug-sensitive and drug-tolerant persister phenotypes has been proposed to play a key role in non-genetic resistance to therapy. Yet, we show here that cancer cells actually possess a highly stable inherited chance to persist (CTP) during therapy. This CTP is non-stochastic, determined pre-treatment, and has a unimodal distribution ranging from 0 to almost 100%. Importantly, CTP is drug-specific. We found that differential serine/threonine phosphorylation of the insulin receptor substrate 1 (IRS1) protein determines the CTP of lung and of head and neck cancer cells under EGFR inhibition, both in vitro and in vivo. Indeed, the first-in-class IRS1 inhibitor NT219 was highly synergistic with anti-EGFR therapy across multiple in vitro and in vivo models. Elucidation of drug-specific mechanisms that determine the degree and stability of cellular CTP may establish a framework for the elimination of cancer persisters, using novel rationally designed drug combinations.
HostingRepository	PRIDE
AnnounceDate	2025-11-03
AnnouncementXML	Submission_2025-11-03_03:52:38.186.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Geiger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-21 03:04:13	ID requested
1	2021-06-22 04:11:18	announced
⏵ 2	2025-11-03 03:52:39	announced	2025-11-03: Updated project metadata.

Jacob Berger A, Gigi E, Kupershmidt L, Meir Z, Gavert N, Zwang Y, Prior A, Gilad S, Harush U, Haviv I, Stemmer SM, Blum G, Merquiol E, Mardamshina M, Kaminski Strauss S, Friedlander G, Bar J, Kamer I, Reizel Y, Geiger T, Pilpel Y, Levin Y, Tanay A, Barzel B, Reuveni H, Straussman R, IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy. Nat Cancer, 2(10):1055-1070(2021) [pubmed]

10.1038/s43018-021-00261-1;

submitter keyword: IRS1, drug tolerant cells, drug resistance, EGFR inhibition, NSCLC,Cancer, cancer persisters

Geiger Tamar
contact affiliation	Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
contact email	geiger@tauex.tau.ac.il
lab head
Tamar Geiger
contact affiliation	Weizmann Institute of Science
contact email	geiger@tauex.tau.ac.il
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/2021/06/PXD026834

PRIDE project URI

• PRIDE
  1. PXD026834
     1. Label: PRIDE project
     2. Name: IRS1 phosphorylation determines a heritable probability of cancer cells to persist during EGFR inhibition therapy