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PXD026834 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIRS1 phosphorylation determines a heritable probability of cancer cells to persist during EGFR inhibition therapy
DescriptionStochastic 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.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTamar Geiger
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-06-21 03:04:13ID requested
12021-06-22 04:11:18announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Cancer, drug tolerant cells, cancer persisters, drug resistance, EGFR inhibition, IRS1, NSCLC
Contact List
Geiger Tamar
contact affiliationDepartment of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
contact emailgeiger@tauex.tau.ac.il
lab head
Tamar Geiger
contact affiliationTel Aviv University
contact emailgeiger@tauex.tau.ac.il
dataset submitter
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Dataset FTP location
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