Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1219682 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32243220_1.fastq.gz | Fastqsanger.gz | |||
| SRR32243220_2.fastq.gz | Fastqsanger.gz | |||
| SRR32243221_1.fastq.gz | Fastqsanger.gz | |||
| SRR32243221_2.fastq.gz | Fastqsanger.gz | |||
| SRR32243222_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Antigenic cancer persister cells survive direct T cell attack
| PRJNA1219558 | ENA
Project description:Drug-tolerant cancer persister cells were reported fifteen years ago as cells in a quiescent, reversible cell state which tolerates unattenuated cytotoxic drug stress. It remains unknown whether a similar phenomenon contributes to immune evasion. Here we report an antigenic persister state which survives weeks of cytotoxic T lymphocyte (CTL) attack. In contrast to immune evasion mechanisms that limit immune detection or activation, antigenic persisters robustly activate CTLs which deliver Granzyme B, secrete IFNγ, induce tryptophan starvation, and initiate persister cell apoptosis. However, instead of dying, persisters paradoxically leverage apoptotic stress to suppress inflammatory death and acquire mutations and epigenetic changes which enable outgrowth of CTL-resistant cells. Furthermore, persister cells undergoing sublethal apoptosis are enriched in inflamed human and mouse tumors which have regressed during immunotherapy. These findings reveal that adaptive evolution mediated by persister cells surviving direct T cell attack presents a barrier to complete immune-mediated tumor rejection.
2025-04-15 | GSE288822 | GEO
Project description:Acquired drug resistance prevents targeted cancer therapy from achieving stable and complete responses. Emerging evidence implicates a key role for nonmutational mechanisms including changes in cell state during early stages of acquired drug resistance. Targeting nonmutational resistance may therefore present a therapeutic opportunity to eliminate residual surviving tumor cells and impede relapse. A variety of cancer cell lines harbor quiescent, reversibly drug-tolerant âpersisterâ cells which survive cytotoxic drugs including targeted therapies and chemotherapies. These persister cells survive drug through nonmutational mechanisms which are poorly understood. Specifically targeting persister cells is a promising strategy to prevent tumor relapse. We sought to identify therapeutically exploitable vulnerabilities in persister cells using the HER2-amplified breast cancer line BT474 as an experimental model. Similar to other persister cell models, upon treatment with the HER2 inhibitor lapatinib (2uM concentration) for nine or more days, the majority of BT474 cells die, revealing a small population of quiescent surviving persister cells. Removal of lapatinib allows the persister cells to regrow and to re-acquire sensitivity to lapatinib. Subsequent lapatinib treatment re-derives persister cells. The reversibility of persister cell drug resistance indicates a nonmutational resistance mechanism. Here we provide RNAseq gene expression profiling data generated from parental BT474 cells compared to BT474 persister cells generated from nine days of treatment with 2 uM lapatinib. These data can be used to identify genes and pathways which are upregulated in persister cells, revealing potential therapeutic targets. 3 biological replicates of BT474 persister cells, two biological replicates of BT474 parental cells
2016-07-28 | E-GEOD-84896 | biostudies-arrayexpress
Project description:Acquired drug resistance prevents targeted cancer therapy from achieving stable and complete responses. Emerging evidence implicates a key role for nonmutational mechanisms including changes in cell state during early stages of acquired drug resistance. Targeting nonmutational resistance may therefore present a therapeutic opportunity to eliminate residual surviving tumor cells and impede relapse. A variety of cancer cell lines harbor quiescent, reversibly drug-tolerant “persister” cells which survive cytotoxic drugs including targeted therapies and chemotherapies. These persister cells survive drug through nonmutational mechanisms which are poorly understood. Specifically targeting persister cells is a promising strategy to prevent tumor relapse. We sought to identify therapeutically exploitable vulnerabilities in persister cells using the HER2-amplified breast cancer line BT474 as an experimental model. Similar to other persister cell models, upon treatment with the HER2 inhibitor lapatinib (2uM concentration) for nine or more days, the majority of BT474 cells die, revealing a small population of quiescent surviving persister cells. Removal of lapatinib allows the persister cells to regrow and to re-acquire sensitivity to lapatinib. Subsequent lapatinib treatment re-derives persister cells. The reversibility of persister cell drug resistance indicates a nonmutational resistance mechanism. Here we provide RNAseq gene expression profiling data generated from parental BT474 cells compared to BT474 persister cells generated from nine days of treatment with 2 uM lapatinib. These data can be used to identify genes and pathways which are upregulated in persister cells, revealing potential therapeutic targets.
2016-07-28 | GSE84896 | GEO
Project description:Oncogene targeted cancer therapies can provide deep responses but frequently suffer from acquired resistance. Therapeutic approaches to treat tumours which have acquired drug resistance are complicated by continual tumour evolution and multiple co-occurring resistance mechanisms. Rather than treating resistance after it emerges, it may possible to prevent it by inhibiting the adaptive processes which initiate resistance but these are poorly understood. Here we report that residual cancer persister cells that survive oncogene targeted therapy are growth arrested by drug stress-induced intrinsic Type I interferon (IFN) signaling. To escape growth arrest, persister cells leverage apoptotic machinery to transcriptionally suppress interferon-stimulated genes (ISGs). Mechanistically, persister cells sublethally engage apoptotic caspases to activate DNA endonuclease DNA Fragmentation Factor B (DFFB, also known as Caspase-Activated DNase (CAD)) which induces DNA damage, mutagenesis, and stress response factor Activating Transcription Factor 3 (ATF3). ATF3 limits Activator Protein-1 (AP1)-mediated ISG expression sufficiently to allow persister cell regrowth. Persister cells deficient in DFFB or ATF3 exhibit high ISG expression and are consequently unable to regrow. Therefore, sublethal apoptotic stress paradoxically promotes regrowth of residual cancer cells that survive drug treatment.
2025-04-10 | GSE196018 | GEO
Project description:Targeted therapies require life-long treatment, as drug discontinuation invariably leads to tumor recurrence. Recurrence is thought to mainly be driven by minor subpopulations of drug tolerant persister (DTP) cells that survive the cytotoxic drug effect. In lung cancer, DTP studies have mainly been conducted using tumor cell line models.
2022-12-21 | GSE199716 | GEO
Project description:When bacteria are challenged with antimicrobials, small numbers of cells may survive treatment. These so-called persister cells are not mutants, but are a set of phenotypic variants which, after re-growth exhibit the same susceptibility properties as their progenitor populations. The presence of persisters may determine the effective therapeutic dose of antibiotics and account for the intractability of biofilm-related infections. In the current investigation, Escherichia coli persister cells were isolated without prior exposure to antimicrobials, using fluorescence-assisted cell sorting of a strain, labelled with a chromosomal green fluorescent protein marker. Levels of persistence were inversely proportional to fluorescence intensity in the gfp-tagged E. coli population, and separated persister cells showed enhanced expression of two groups of genes located in the e14 and CP4-6 cryptic prophage regions when analysed by DNA microarray.
2013-10-13 | E-MEXP-3511 | biostudies-arrayexpress
Project description:Drug-tolerant “persister” cells underlie the emergence of drug-resistant clones and allow residual tumors to survive therapy; thus, represent an attractive therapeutic target to mitigate relapse. With the promising outcome, yet some resistance cases surfaced after the approval of venetoclax (ABT-199), we defined a novel invasive drug resistance mechanism induced by Bcl2 inhibitor via examining the evolution of drug tolerant persister clones generated with ABT-199 treatment. The ABT-199 drug-tolerant persister cells showed genetic alteration by losing the copy number at 18q21 paralleled with BCL2, PMAIP1 and TCF4 gene downregulation. The persister status are generated through major enhancer-remodeling mediated transcriptional activation of the super enhancer, which offered unique opportunity for overcoming the drug resistance. The insight of major determinant for ABT-199 persistence evolution identified the molecular vulnerability in Bcl2 inhibitor resistant lymphoma cells through CDK7 pathway inhibition. The combined CDK7 and BCL2 inhibition was found to be more effective against ABT-199 persistence ex vivo and in vivo rather than the parental line, and CDK7 inhibition eliminated the persister phenotype by blocking dynamic active enhancer formation to further prevent the evolution of drug resistance. Together, these studies unified genetic alteration and non-mutational adaptive response as a drug resistance mechanism, more importantly, demonstrated a rationale for transcriptional inhibition-based combination strategies to prevent and overcome drug resistance in B-cell malignancies.
2019-05-01 | GSE116097 | GEO
Project description:Most genetic events that drive melanoma development and resistance to targeted therapy have been uncovered. In contrast, and despite their increasingly recognized contribution, little is known about the non-genetic mechanisms that drive these processes. Here, we performed in vivo gain-of-function CRISPR screens and identified SMAD3, BIRC3 and SLC9A5 as key drivers of BRAFi-resistance and the tumor growth capability of persister cells. We show that their expression levels increase during acquisition of BRAFi-resistance, and remain high in persister cells and during relapse. Critically, chemical inhibition of SMAD3 or BIRC3 efficiently abrogates melanoma tumor growth and persister cells proliferation. Genetic inhibition of these targets efficiently restored the sensitivity of persister cells to BRAFi. Our work expands our understanding of the biology of persister cells and highlight novel drug vulnerabilities that can be exploited to develop long-lasting anti-melanoma therapies.
2021-02-03 | E-MTAB-8595 | biostudies-arrayexpress
Project description:Tumors consist of heterogeneous cell population, containing cancer cell subpopulations with anticancer drug-resistant property, called “persister” cells. To reveal the character of the persister cells, we analyzed gene expression profile of patient-derived gastric cells and residual cancer cells after treatment with 5-FU or SN38, an active metabolite of irinotecan. In our study, we identified ALDH1A3 as a marker and a cell proliferation factor of persister cells. To examine molecular pathways regulated by ALDH1A3, we analyzed gene expression profile of patient-derived gastric JSC15-3 in which ALDH1A3 was knocked down by using shRNAs.
2020-04-14 | GSE139331 | GEO