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IRS1 phosphorylation determines a heritable probability of cancer cells to persist during EGFR inhibition therapy [Mars-seq]

ABSTRACT: IRS1 phosphorylation determines a heritable probability of cancer cells to persist during EGFR inhibition therapy [Mars-seq]

PROVIDER: PRJNA742903 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15012845_1.fastq.gz	Fastqsanger.gz
	SRR15012845_2.fastq.gz	Fastqsanger.gz
	SRR15012846_1.fastq.gz	Fastqsanger.gz
	SRR15012846_2.fastq.gz	Fastqsanger.gz

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IRS1 phosphorylation determines a heritable probability of cancer cells to persist during EGFR inhibition therapy

Project 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.

2021-06-22 | PXD026834 | Pride

IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy [Exp2]

Project description:We found that differential serine/threonine phosphorylation of the insulin receptor substrate 1 (IRS1) protein determines the chance to persist (CTP) of lung and of head and neck cancer cells under EGFR inhibition, both in vitro and in vivo.

2021-08-09 | GSE178976 | GEO

IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy [Exp1]

2021-08-09 | GSE178975 | GEO

IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy [Exp3]

2021-08-09 | GSE178977 | GEO

IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy.

Project description:IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy.

| PRJNA741779 | ENA

IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy [Exp2]

Project description:IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy [Exp2]

| PRJNA741783 | ENA

IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy [Exp1]

Project description:IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy [Exp1]

| PRJNA741781 | ENA

IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy [Exp3]

Project description:IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy [Exp3]

| PRJNA741782 | ENA

IRS1 phosphorylation determines a heritable probability of cancer cells to persist during EGFR inhibition therapy [Mars-seq]

Project description:As part of a multi-omic pursuit for mechanisms of persistency of cancer cells to drug treatment, we generated pair-wise transcriptome analysis of nearly 200 single-cell-derived clonal populations, with and w/o drug treatment.

2021-07-05 | GSE179240 | GEO

IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy

2021-08-10 | PXD026824 | Pride