Ontology highlight
ABSTRACT:
PROVIDER: PRJNA907280 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22479945_1.fastq.gz | Fastqsanger.gz | |||
| SRR22479945_2.fastq.gz | Fastqsanger.gz | |||
| SRR22479946_1.fastq.gz | Fastqsanger.gz | |||
| SRR22479946_2.fastq.gz | Fastqsanger.gz | |||
| SRR22479947_1.fastq.gz | Fastqsanger.gz |
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Project description:Elevated methionine flux drives pyroptosis evasion in persister cancer cells
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Project description:Induction of cell death represents a primary goal of most anti-cancer treatments. Despite the efficacy of such approaches, a small population of “persisters” develop evasion strategies to therapy-induced cell death. While previous studies have identified mechanisms of resistance to apoptosis, the mechanisms by which persisters dampen other forms of cell death, such as pyroptosis, remain to be elucidated. Pyroptosis is a form of inflammatory cell death that involves formation of membrane pores, ion gradient imbalance, water inflow and membrane rupture. Herein, we investigate mechanisms by which cancer persisters resist pyroptosis, survive, then proliferate in the presence of tyrosine kinase inhibitors (TKI). Lung, prostate and esophageal cancer persister cells remaining after treatments exhibited several hallmarks indicative of pyroptosis resistance. The inflammatory attributes of persisters included chronic activation of inflammasome, STING, and type I interferons. Comprehensive metabolomic characterization uncovered that TKI-induced pyroptotic persisters display high methionine consumption and excessive taurine production. Elevated methionine flux or exogenous taurine maintained plasma membrane integrity via osmolyte-mediated effects. Increased dependency on methionine flux decreased the level of one carbon metabolism intermediate S-(5'-adenosyl)-L-homocysteine, a determinant of cell methylation capacity. The consequent increase in methylation potential induced DNA hypermethylation of genes regulating metal ion balance and intrinsic immune response. This enabled thwarting TKI resistance by using the hypomethylating agent decitabine. In summary, the evolution of resistance to pyroptosis can occur via a stepwise process of physical acclimation and epigenetic changes without existing or recurrent mutations.
2022-12-02 | GSE219044 | GEO
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:Thioridazine exhibits inhibitory effects on various tumors, including epithelial ovarian cancer, but the mechanisms remain unclear. Proliferation and invasion were assessed using CCK8 and Matrigel invasion assays. Autophagy and pyroptosis-related markers were detected via Western blot. Autophagy flux was tracked using the mRFP-GFP-LC3 reporter. Autophagy inhibitors 3MA andBufA1 were used to confirm whether autophagy flux was functioning properly. RNA sequencing was performed to identify differentially expressed genes, and Co-IP was used to detect interacting proteins. A subcutaneous tumorigenesis experiment in nude mice was conducted to evaluate the effect of thioridazine in vivo. As a result, thioridazine inhibited proliferation and invasion of EOC while promoting autophagy and pyroptosis. The upregulation of the pyroptosis marker NLRP3 may be attributed to DRD2 inhibition. Inhibition of autophagy enhanced NLRP3 expression, and the autophagy inhibitor CQ increased the tumor-inhibiting effects of thioridazine. In conclusion, thioridazine inhibited EOC proliferation and invasion by inducing pyroptosis and autophagy, with autophagy playing a protective role in thioridazine treatment. Thioridazine combined with the autophagy inhibitor CQ may be an effective treatment for EOC.
2025-04-24 | GSE295565 | GEO
Project description:We describe a function of focal adhesion kinase (FAK) in driving anti-tumor immune evasion. The kinase activity of nuclear-targeted FAK in squamous cancer cells drives exhaustion of CD8+ T-cells and recruitment of regulatory T-cells by transcriptionally regulating chemokine/cytokine and ligand-receptor networks, including transcription of Ccl5 that is crucial. These changes inhibit antigen-primed cytotoxic CD8+ T-cell activity, permitting growth of FAK-expressing tumors. To address how FAK activity in squamous cell carcinoma (SCC) cancer cells promotes elevated intra-tumoral regulatory T-cells, we analyzed global transcriptional profiles of SCC cells expressing or not expressing FAK.
2015-09-29 | GSE71662 | 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:ZNF296 drives immune evasion in epithelial cancer cells [ChIP-seq]
| PRJNA1191519 | ENA
Project description:ZNF296 drives immune evasion in epithelial cancer cells [RNA-seq]
| PRJNA1191517 | ENA
Project description:ZNF296 drives immune evasion in epithelial cancer cells [ATAC-seq]
| PRJNA1191518 | ENA
Project description:Metabolomics raw LCMS files for Figure 1D-1F. Schofield et al, Cell Reports, "Acod1 Expression in Cancer Cells Promotes Immune Evasion through the Generation of Inhibitory Peptides".
2024-03-03 | MSV000094226 | GNPS