Expression data of tigecycline-treated liver cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE199842 | GEO | 2022/04/26
REPOSITORIES: GEO
Similar Datasets
Project description:Haplo-insufficiency profiling followed by Gene-set enrichment analysis of sensitive strains was conducted in yeast treated with tigecycline. This revealed significant enrichment of genes involved in mitochondrial translation, similar to that seen with the known mitochondrial translation inhibitors chloramphenicol and linezolid
2011-11-01 | E-MTAB-814 | biostudies-arrayexpress
Project description:Through an shRNA screen we have identified Prmt1 as a genetic vulnerability of p53/Rb-null murine osteosarcoma cells. Depletion of Prmt1 in p53-deficient cells impairs tumor initiation and maintenance in vitro and in vivo. Mechanistic studies reveal that translation-associated pathways are enriched for Prmt1 downstream targets, implicating a role of Prmt1 in translation control. In particular, we have shown that loss of Prmt1 leads to a the decrease in arginine methylation of the translation initiation complex, thereby disrupting its assembly and inhibiting translation. We also observed that p53/Rb-null cells are sensitive to p53-induced translation stress. Analysis of the human tumor cell Achilles data set further reveals that Prmt1 and translation-associated pathways converge on the same functional networks. We propose that targeted therapy directed to inhibition of Prmt1 and its associated translation-related pathways represents a novel and promising therapeutic strategy for p53-deficient cancer cells that exhibit dependencies on translation stress response.
2018-01-06 | GSE93309 | GEO
Project description:Multiple myeloma is an incurable hematological malignancy evolving from precursor states to advanced phases of the disease. MYC abnormalities play a critical role in the disease progression. Nevertheless, MYC lacks therapeutic drugability, thereby necessitating the exploration of alternative strategies aimed at circumventing the challenges associated with targeting MYC. In this study, we hypothesized that MYC upregulation induces genomic dependencies in tumor cells, creating vulnerabilities that can be exploited therapeutically. We discovered a differential dependency on glutamine metabolism in MYC overexpressing cells. We functionally explored these dependencies as a selective targetable vulnerability in vitro and in vivo. Furthermore, we uncovered a potential synergistic combination that can exacerbated this metabolic vulnerability, Collectively, our in vitro and in vivo results revealed an effective therapeutic combinatory strategy in the context of MYC overexpressing MM.
2024-04-09 | PXD050010 | Pride
Project description:Tigecycline, a protein translation inhibitor, is a treatment of last resort for infections caused by the opportunistic multidrug resistant human pathogen Acinetobacter baumannii. However, strains resistant to tigecycline were reported not long after its clinical introduction. Translation inhibitor antibiotics perturb ribosome function and induce the reduction of (p)ppGpp, an alarmone involved in the stringent response that negatively modulates ribosome production. Through RNA sequencing, this study revealed a significant reduction in the transcription of genes in citric acid cycle and cell respiration, suggesting tigecycline inhibits or slows down bacterial growth. Our results indicated that the drug-induced reduction of (p)ppGpp level promoted the production but diminished the degradation of ribosomes, which mitigates the translational inhibition effect by tigecycline. The reduction of (p)ppGpp also led to a decrease of transcription coupled nucleotide excision repair which likely increases the chances of development of tigecycline resistant mutants. Increased expression of genes linked to horizontal gene transfer were also observed. The most upregulated gene, rtcB, involving in RNA repair, is either a direct tigecycline stress response or is in response to the transcription de-repression of a toxin-antitoxin system. The most down-regulated genes encode two b-lactamases, which is a possible by-product of tigecycline-induced reduction in transcription of genes associated with peptidoglycan biogenesis. This transcriptomics study provides a global genetic view of why A. baumannii is able to rapidly develop tigecycline resistance.
2020-08-03 | GSE131451 | GEO
Project description:Background. Many age-associated disorders (including diabetes, cancer, and neurodegenerative diseases) have been linked to mitochondrial dysfunction, which leads to impaired cellular bioenegetics (decreased ATP production) and increased oxidative stress. However, it is not known what genetic and molecular pathways underlie differential vulnerability to mitochondrial dysfunction observed among different cell types. Methodology/Principal Findings. Starting with CRI-G1 insulinoma cells as a model of a neuronal/endocrine cell type, we isolated a novel (CRI-G1-RS) cell line that was more susceptible to cell death induced by mitochondrial respiratory chain inhibitors or direct oxidants than the parental CRI-G1 cell line (for clarity renamed CRI-G1-RR). In contrast, RS cells were equally vulnerable to mitochondrial uncoupling and less vulnerable to protein kinase inhibition than RR cells, suggesting that differences in vulnerability to mitochondrial toxins among the two cell types did not stem from differences in ATP production/utilization or in downstream apoptotic machinery. Genome-wide gene expression analysis and follow-up biochemical studies revealed that, in this experimental system, increased vulnerability to mitochondrial and oxidative stress was associated with (1) inhibition of ARE/Nrf2/Keap1 antioxidant pathway; (2) decreased expression of antioxidant and phase I/II conjugation enzymes, most of which are Nrf2 transcriptional targets; (3) increased expression of molecular chaperones, many of which are also considered Nrf2 transcriptional targets; and (4) increased expression of β cell-specific genes and transcription factors that specify/maintain β cell fate. Conclusions/Significance. The molecular profile presented here will enable identification of individual genes and/or gene clusters that shape vulnerability to mitochondrial dysfunction and thus represent potential therapeutic targets for diabetes and neurodegenerative diseases. In addition, the newly identified CRI-G1-RS cell line represents a new experimental model for investigating how endogenous antioxidants affect glucose sensing and insulin release by pancreatic β cells. Six biological replicates for each of two cell types (12 samples total)
2010-08-31 | E-GEOD-19948 | biostudies-arrayexpress
Project description:Multiple myeloma is an incurable hematological malignancy evolving from precursor states to advanced phases of the disease. MYC abnormalities play a critical role in the disease progression. Nevertheless, MYC lacks therapeutic drugability, thereby necessitating the exploration of alternative strategies aimed at circumventing the challenges associated with targeting MYC. In this study, we hypothesized that MYC upregulation induces genomic dependencies in tumor cells, creating vulnerabilities that can be exploited therapeutically. We discovered a differential dependency on glutamine metabolism in MYC overexpressing cells. We functionally explored these dependencies as a selective targetable vulnerability in vitro and in vivo. Furthermore, we uncovered a potential synergistic combinations that can exacerbated this metabolic vulnerability, Collectively, our in vitro and in vivo results revealed an effective therapeutic combinatory strategy in the context of MYC overexpressing MM.
2023-09-04 | GSE241948 | GEO
Project description:Expression data of tigecycline-treated liver cancer cells
| PRJNA821687 | ENA
Project description:The metabolic dependencies of cancer cells have significant potential to be exploited to improve the diagnosis and treatment of cancer. Creatine riboside (CR) is a novel urinary metabolite associated with risk and prognosis in lung and liver cancer. However, the source of high creatine riboside levels in cancer patients, as well as its implications for the treatment of these aggressive cancers remain unclear. By integrating RNA sequencing and whole exome sequencing of non-small cell lung cancer tissues we sought to understand the source of creatine riboside and the tumor biology associated with this novel metabolite. Utilising multiple lung and liver cancer cohorts, next generation sequencing data was combined with global metabolomics analysis of human tumors, and matched liquid biopsies together with functional studies to reveal that dysregulation of the mitochondrial urea cycle and nucleotide imbalance are associated with high creatine riboside levels and are indicators of poor prognosis. Creatine riboside-high cancer cells were auxotrophic for arginine, revealing a metabolic vulnerability that may be exploited therapeutically. This highlights the potential of creatine riboside not only as a poor prognosis biomarker but also as a companion biomarker to inform the administration of arginine-targeted therapies in precision medicine strategies to improve cancer patient survival.
2022-04-24 | GSE201221 | GEO
Project description:Here, we reveal that mitochondrial tRNA methylation is essential for efficient mitochondrial translation to dynamically shape cancer metabolism required for metastasis. Using oral squamous cell carcinoma (OSCC, SCC25 from ATCCR CRL-168TM and patient-derived cell lines with the names VDH01, VDH15) as a model system, we reveal the metabolic requirements of the metastasis-initiating tumour cell population. Only non-dividing tumour cells with high mitochondrial translation rates can invade and disseminate from primary tumours. Thus, inhibition of mitochondrial translation either through deletion of NSUN3 or through pharmacological inhibitors both block metastasis in orthotopic transplantation assays. Together, our study demonstrates that mitochondrial translation controls the metabolic reprogramming required for invasion and dissemination from the primary tumour.
| EGAS00001004765 | EGA
Project description:Purpose: FBXW7 is one of the most frequently mutated tumor suppressors, the deficiency of which has been associated with resistance to some anticancer therapies. Through bioinformatic analyses and genome-wide CRISPR screens, we here reveal that FBXW7 deficiency leads to multi-drug resistance (MDR), to a bigger extent than well-established MDR-drivers such as ABCB1. Proteomic data from FBXW7-deficient cells and human cancer samples identify the upregulation of mitochondrial function as a hallmark of FBXW7 deficiency, which has been previously linked to an increased resistance to chemotherapy. Accordingly, genetic or chemical targeting of mitochondria is preferentially toxic for FBXW7-deficient cells. For instance, targeting mitochondrial translation with the antibiotic Tigecycline efficiently kills FBXW7-deficient cells in vitro and in vivo, by a mechanism that involves activation of the Integrated Stress Response (ISR). Searching for additional drugs that overcome MDR in FBXW7-deficient cells, we found several targeted therapies such as Erlotinib, Dasatinib or Vemurafenib which unexpectedly also activate the ISR. Together, our study reveals that one of the most frequent mutations in cancer reduces the sensitivity to the vast majority of available therapies, and identifies a general principle to overcome such resistance. Methods: This study was performed in 2 groups of DLD1 cells with duplicate samples per group. Both control (Wild Type, WT) and experimental (FBXW7 -/-, KO) were exposed to Tigecycline (10µM). DMSO was used as a control for the treatment. After 24h, the RNA was extracted and the transcriptome was profiled with RNA-Sequencing (RNA-seq) analysis. Results: our study reveals that one of the most frequent mutations in cancer reduces the sensitivity to the vast majority of available therapies, and identifies a general principle to overcome such resistance.
2022-06-09 | GSE189499 | GEO