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:Cancer persister cells which survive oncogene targeted therapies are sensitized to ferroptosis but mechanistic understanding of this vulnerability remains limited. Here, we found that while levels of iron, glutathione and various ferroptosis suppressing enzymes vary among persister cell types, ferroptosis suppressor protein 1 (FSP1) is downregulated in multiple persister cell types and persister cells which survive glutathione peroxidase 4 (GPX4) inhibition rely upon residual FSP1 to survive. Furthermore, persister cells which survive GPX4 inhibition downregulate oxidative phosphorylation, a key source of mitochondrial reactive oxygen species which are required for persister cell ferroptosis. We also found that persister cell treatment with histone deacetylase inhibitors induce reactive oxygen species and sensitize multiple persister cell types to GPX4 inhibition. Together, these findings reveal that FSP1 and histone deacetylases suppress persister cell ferroptosis.
2025-11-10 | GSE303411 | 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:Chemotherapy often kills a large fraction of cancer cells but leaves behind a small population of drug-tolerant persister cells. These persister cells survive drug treatments through reversible, non-genetic mechanisms and cause tumour recurrence upon cessation of therapy. Here, we report a drug tolerance mechanism regulated by the germ-cell-specific H3K4 methyltransferase PRDM9. Through histone proteomic, transcriptomic, lipidomic, and ChIP-sequencing studies combined with CRISPR knockout and phenotypic drug screen, we identified that chemotherapy-induced PRDM9 upregulation promotes metabolic rewiring in glioblastoma stem cells, leading to chemotherapy tolerance. Mechanistically, PRDM9-dependent H3K4me3 at cholesterol biosynthesis genes enhances cholesterol biosynthesis, which persister cells rely on to maintain homeostasis under chemotherapy-induced oxidative stress and lipid peroxidation. PRDM9 inhibition, combined with chemotherapy, resulted in strong anti-cancer efficacy in preclinical glioblastoma models, significantly enhancing the magnitude and duration of the antitumor response by eliminating persisters. These findings demonstrate a previously unknown role of PRDM9 in promoting metabolic reprogramming that enables the survival of drug-tolerant persister cells.
2025-09-30 | GSE262377 | GEO
Project description:Chemotherapy often kills a large fraction of cancer cells but leaves behind a small population of drug-tolerant persister cells. These persister cells survive drug treatments through reversible, non-genetic mechanisms and cause tumour recurrence upon cessation of therapy. Here, we report a drug tolerance mechanism regulated by the germ-cell-specific H3K4 methyltransferase PRDM9. Through histone proteomic, transcriptomic, lipidomic, and ChIP-sequencing studies combined with CRISPR knockout and phenotypic drug screens, we identified that chemotherapy-induced PRDM9 upregulation promotes metabolic rewiring in glioblastoma stem cells, leading to chemotherapy tolerance. Mechanistically, PRDM9-dependent H3K4me3 at cholesterol biosynthesis genes enhances cholesterol biosynthesis, which persister cells rely on to maintain homeostasis under chemotherapy-induced oxidative stress and lipid peroxidation. PRDM9 inhibition, combined with chemotherapy, resulted in strong anti-cancer efficacy in preclinical glioblastoma models, significantly enhancing the magnitude and duration of the antitumor response by eliminating persisters. These findings reveal a previously unknown role of PRDM9 in promoting metabolic reprogramming that enables the survival of drug-tolerant persister cells.
2025-09-30 | GSE279413 | 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:Chemotherapy often kills a large fraction of cancer cells but leaves behind a small population of drug-tolerant persister cells. These persister cells survive drug treatments through reversible, non-genetic mechanisms and cause tumour recurrence upon cessation of therapy. Here, we report a drug tolerance mechanism regulated by the germ-cell-specific H3K4 methyltransferase PRDM9. Through histone proteomic, transcriptomic, lipidomic, and ChIP-sequencing studies combined with CRISPR knockout and phenotypic drug screens, we identified that chemotherapy-induced PRDM9 upregulation promotes metabolic rewiring in glioblastoma stem cells, leading to chemotherapy tolerance. Mechanistically, PRDM9-dependent H3K4me3 at cholesterol biosynthesis genes enhances cholesterol biosynthesis, which persister cells rely on to maintain homeostasis under chemotherapy-induced oxidative stress and lipid peroxidation. PRDM9 inhibition, combined with chemotherapy, resulted in strong anti-cancer efficacy in preclinical glioblastoma models, significantly enhancing the magnitude and duration of the antitumor response by eliminating persisters. These findings reveal a previously unknown role of PRDM9 in promoting metabolic reprogramming that enables the survival of drug-tolerant persister cells.
2025-09-30 | GSE279420 | GEO