PXD026824 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | IRS1 phosphorylation underlies the non-stochastic 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 | 2021-08-10 |
AnnouncementXML | Submission_2021-08-10_00:43:45.389.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Amir Prior |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive HF; Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-06-21 03:03:30 | ID requested | |
⏵ 1 | 2021-08-10 00:43:45 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Cancer, drug tolerant cells, cancer peristers, drug resistance, EGFR inhibition, IRS1, NSCLC |
Contact List
Ravid Straussman |
contact affiliation | Department of Molecular Cell Biology, Weizmann institute of Science, Israel |
contact email | Ravidst@weizmann.ac.il |
lab head | |
Amir Prior |
contact affiliation | Weizmann Institute of Science |
contact email | amir.prior@weizmann.ac.il |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD026824
- Label: PRIDE project
- Name: IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy