Single-cell RNAseq profiling of HeLa cells after stimulation with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
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PROVIDER: PRJNA577470 | ENA |
REPOSITORIES: ENA
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Project description:HeLa cells were treated with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL: 10, 25 or 40ng/ml) or with the drug vehicle ("Control"), for 50 minutes or 2 hours prior to analyses by single-cell RNA sequencing. The objective was to study the extent of gene expression variability in resting cells and to evaluate the effect of time and dose of TRAIL treatments on gene expression variability.
2020-09-23 | GSE138833 | GEO
Project description:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to be a potent inducer of apoptosis in various cancer cell lines and primary cancer cells. However, in clinical trials administration of recombinant TRAIL or TRAIL death receptor agonists did not show sufficient efficacy for treatment of tested malignant disorders compared to standard chemotherapy. Acquired resistance of cancer cells to TRAIL and to other âdeath receptorâ ligands may explain not only the inability of TRAIL and TRAIL âdeath receptorâ agonists to achieve the clearance of cancer cells in vivo but also the escape of cancer cells from immune cell â mediated killing. Selective pressure of TRAIL on TRAIL-sensitive Jurkat T-lymphoblastic leukemia cells provided several TRAIL resistant Jurkat cell line clones (TR1, TR2, TR3). We showed that acquired TRAIL resistance was associated with complex disruption of both extrinsic and intrinsic apoptotic pathways manifested by acquired multi-drug resistant phenotype of TR1, TR2, and TR3 clones. To identify changes associated with TRAIL resistance of Jurkat cells we performed genome-wide gene expression analysis of TRAIL-resistant clones (TR) and compared to WT Jurkat cells. We identified significantly increased expression (1.33-fold change with adjusted p < 0.05) of 73 genes in TR1 clone, 53 genes in TR2 clone and 8 genes in TR3 clone, and significant decrease in expression (0.75-fold change with adjusted p < 0.05) of 174 genes in TR1 clone, 36 genes in TR2 clone and 28 genes in TR3 clone. There was an overlap of only 2 significantly overexpressed (midkine / MDK and zinc finger and BTB domain containing 16 gene / ZBTB16 / PLZF) and 4 downregulated genes (YAP1, IGJ, EIF1AY, RPS4Y1) in all three TR clones. Total cellular RNA was isolated from biologic duplicates of untreated Jurkat cells (WT) and TRAIL resistant Jurkat cell line subclones (TR1, TR2, TR3) established by selective pressure of TRAIL 1000 ng/mL on Jurkat cells over the period of 12 weeks.
2016-06-15 | E-GEOD-38743 | biostudies-arrayexpress
Project description:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to be a potent inducer of apoptosis in various cancer cell lines and primary cancer cells. However, in clinical trials administration of recombinant TRAIL or TRAIL death receptor agonists did not show sufficient efficacy for treatment of tested malignant disorders compared to standard chemotherapy. Acquired resistance of cancer cells to TRAIL and to other “death receptor” ligands may explain not only the inability of TRAIL and TRAIL “death receptor” agonists to achieve the clearance of cancer cells in vivo but also the escape of cancer cells from immune cell – mediated killing. Selective pressure of TRAIL on TRAIL-sensitive Jurkat T-lymphoblastic leukemia cells provided several TRAIL resistant Jurkat cell line clones (TR1, TR2, TR3). We showed that acquired TRAIL resistance was associated with complex disruption of both extrinsic and intrinsic apoptotic pathways manifested by acquired multi-drug resistant phenotype of TR1, TR2, and TR3 clones. To identify changes associated with TRAIL resistance of Jurkat cells we performed genome-wide gene expression analysis of TRAIL-resistant clones (TR) and compared to WT Jurkat cells. We identified significantly increased expression (1.33-fold change with adjusted p < 0.05) of 73 genes in TR1 clone, 53 genes in TR2 clone and 8 genes in TR3 clone, and significant decrease in expression (0.75-fold change with adjusted p < 0.05) of 174 genes in TR1 clone, 36 genes in TR2 clone and 28 genes in TR3 clone. There was an overlap of only 2 significantly overexpressed (midkine / MDK and zinc finger and BTB domain containing 16 gene / ZBTB16 / PLZF) and 4 downregulated genes (YAP1, IGJ, EIF1AY, RPS4Y1) in all three TR clones.
2016-06-15 | GSE38743 | GEO
Project description:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to be a potent inducer of apoptosis in various cancer cell lines and primary cancer cells. However, in clinical trials administration of recombinant TRAIL or TRAIL death receptor agonists did not show sufficient efficacy for treatment of tested malignant disorders compared to standard chemotherapy. Acquired resistance of cancer cells to TRAIL and to other âdeath receptorâ ligands may explain not only the inability of TRAIL and TRAIL âdeath receptorâ agonists to achieve the clearance of cancer cells in vivo but also the escape of cancer cells from immune cell â mediated killing. Selective pressure of TRAIL on TRAIL-sensitive Jurkat T-lymphoblastic leukemia cells provided several TRAIL resistant Jurkat cell line clones (TR1, TR2, TR3). Irrespective of molecular changes histone deacetylase inhibitors (HDACi), such as suberoylanilide-hydroxamic acid (SAHA, vorinostat), were able to restore sensitivity of all three TRAIL-resistant clones to TRAIL. Gene expression analysis of TR1 clone treated with SAHA 1microM for 12 hours compared to untreated TR1 clone showed significant decrease in expression of CFLAR/cFLIP (0.71; p=0.006), BIRC5/survivin (0.80; p=0.024) and BID (0.66; p<0.001). Expression of both TRAIL âdeathâ receptors DR4 (1.57; p<0.001) and DR5 (1.47; p=0.002) were significantly increased compared to untreated TR1 cells. The mRNA expression of caspases-2,-3,-8,-9,-10 did not significantly change with the SAHA treatment. Total cellular RNA was isolated from biologic duplicates of untreated Jurkat cells (WT), TRAIL resistant Jurkat cell clone (TR1) and 1 µM and 0.5 µM suberoylanilide-hydroxamic acid (SAHA, vorinostat) treated TR1 cell clones for 12 hours. Jurkat cell line subclones TR1was established by selective pressure of TRAIL 1000 ng/mL on Jurkat cells over the period of 12 weeks.
2016-06-15 | E-GEOD-38745 | biostudies-arrayexpress
Project description:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to be a potent inducer of apoptosis in various cancer cell lines and primary cancer cells. However, in clinical trials administration of recombinant TRAIL or TRAIL death receptor agonists did not show sufficient efficacy for treatment of tested malignant disorders compared to standard chemotherapy. Acquired resistance of cancer cells to TRAIL and to other “death receptor” ligands may explain not only the inability of TRAIL and TRAIL “death receptor” agonists to achieve the clearance of cancer cells in vivo but also the escape of cancer cells from immune cell – mediated killing. Selective pressure of TRAIL on TRAIL-sensitive Jurkat T-lymphoblastic leukemia cells provided several TRAIL resistant Jurkat cell line clones (TR1, TR2, TR3). Irrespective of molecular changes histone deacetylase inhibitors (HDACi), such as suberoylanilide-hydroxamic acid (SAHA, vorinostat), were able to restore sensitivity of all three TRAIL-resistant clones to TRAIL. Gene expression analysis of TR1 clone treated with SAHA 1microM for 12 hours compared to untreated TR1 clone showed significant decrease in expression of CFLAR/cFLIP (0.71; p=0.006), BIRC5/survivin (0.80; p=0.024) and BID (0.66; p<0.001). Expression of both TRAIL “death” receptors DR4 (1.57; p<0.001) and DR5 (1.47; p=0.002) were significantly increased compared to untreated TR1 cells. The mRNA expression of caspases-2,-3,-8,-9,-10 did not significantly change with the SAHA treatment.
2016-06-15 | GSE38745 | GEO
Project description:To further analyze the change of microRNA (miRNA) between TRAIL-sensitive and TRAIL-resistant Bel-7402 cells Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
2015-10-20 | GSE74130 | GEO
Project description:In this study, we subjected the phenomenon of fractional killing in a clonal population of TRAIL-sensitive cells to careful analysis. We asked whether cells that survive initial exposure to TRAIL are sensitive or resistant to subsequent treatment with TRAIL or other apoptosis-inducing agents. We observed that TRAIL survivor cells were highly resistant to a subsequent treatment with TRAIL 24hr later but that this resistance disappeared following several days in culture. Resistance did not involve downregulation of TRAIL receptors and extended to death ligands that bind different classes of receptors: TRAIL survivors were transiently resistant to FasL and vice versa. Gene expression analysis revealed that NF-kB-mediated inflammatory genes were activated in transiently resistant survivor cells leading to an inflammatory phenotype, but resistance was mediated by an independent mechanism related to changes in signaling at the DISC. Periodic exposure to TRAIL sustained resistance, demonstrating a component of induced survival signaling leading to transient acquired resistance to TRAIL. Based on these results we propose that TRAIL treatment leads to a transient adaptation in survivor cells that can be sustained in cells exposed to long-term TRAIL treatments, leading to acquired resistance. Minimizing the impact of cell-to-cell variability on TRAIL-mediated killing will thus require appropriate spacing of stimuli as well as the use of additional agents that inhibit pro-survival pathways.
2013-07-15 | GSE33340 | GEO
Project description:In this study, we subjected the phenomenon of fractional killing in a clonal population of TRAIL-sensitive cells to careful analysis. We asked whether cells that survive initial exposure to TRAIL are sensitive or resistant to subsequent treatment with TRAIL or other apoptosis-inducing agents. We observed that TRAIL survivor cells were highly resistant to a subsequent treatment with TRAIL 24hr later but that this resistance disappeared following several days in culture. Resistance did not involve downregulation of TRAIL receptors and extended to death ligands that bind different classes of receptors: TRAIL survivors were transiently resistant to FasL and vice versa. Gene expression analysis revealed that NF-kB-mediated inflammatory genes were activated in transiently resistant survivor cells leading to an inflammatory phenotype, but resistance was mediated by an independent mechanism related to changes in signaling at the DISC. Periodic exposure to TRAIL sustained resistance, demonstrating a component of induced survival signaling leading to transient acquired resistance to TRAIL. Based on these results we propose that TRAIL treatment leads to a transient adaptation in survivor cells that can be sustained in cells exposed to long-term TRAIL treatments, leading to acquired resistance. Minimizing the impact of cell-to-cell variability on TRAIL-mediated killing will thus require appropriate spacing of stimuli as well as the use of additional agents that inhibit pro-survival pathways. RNA was collected from Control (untreated) MCF10A cells, Survivors of TRAIL treatment (Day 1), Reset cells (survivors on Day 7), and Repeat cells (Survivors treated with TRAIL on 2 subsequent days). RNA was also collected from Control and Survivor MCF10A cells expressing an IKB-super-repressor construct (Addgene, Plasmid 15291; Boehm et al., 2007), or treated with caspase inhibitors. Three biological experiments were performed (on different days) with 1-2 replicates of each sample collected for each experiment. The total number of samples was 31, on 4 IlluminaRef8 BeadChips (one sample was from an unrelated experiment and was not included). The number of total replicates for each treatment is as follows: Control (7); Survivors (6); Reset (3); Repeat (3); Control-IKB-super-repressor (2); Survivors-IKB-super-repressor (2); Control-zVADinhibitor (2); Survivors-zVADinhibitor (2); Control-IETDinhibitor (2); Survivors-IETDinhibitor (2).
2013-07-15 | E-GEOD-33340 | biostudies-arrayexpress
Project description:To identify intrinsic mechanismis that mediating Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance , gene expression analysis was performed on MDA-MB-231 cell lines exposed to TRAIL, in parental (Sensitive) or treat to resistance (TTR) conditions.
2017-05-29 | GSE82047 | GEO
Project description:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a well-known inducer of apoptosis via formation of the primary death-inducing signaling complex (TRAIL-DISC) at the level of membrane death receptors (DR4 and DR5) which recruit successively FADD and caspase-8. TRAIL can also induce necroptosis when caspases are inhibited. Necroptosis is a regulated cell death dependent on the formation of a cytosolic necrosome complex which includes RIPK1, RIPK3 and MLKL proteins. Elucidating the molecular mechanisms involved in TRAIL-induced necroptosis might provide new insights into the TRAIL death signaling pathway. Here, we report the analysis by mass spectrometry of endogenous RIPK3-dependent necrosome complex constituents upon necroptosis induced by TRAIL/z-VAD/Birinapant (TzB) in HT29 cells. Besides characterization of RIPK1, RIPK3, MLKL, FADD, caspase-8, we find TRIM21 as a new constituent of the necrosome complex. Moreover RIPK1, RIPK3, MLKL, P-MLKL, FADD, caspase-8 and TRIM21 are also found associated to the native TRAIL-DISC upon TzB stimulation showing initiation of the necrotic pathway at the level of TRAIL death receptors in HT29 cells. Finally, TRIM21 may positively modulate necroptosis induction by downregulating NF-kB activation.
2021-03-18 | PXD003383 | Pride