Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chromosomal instability causes sensitivity to polyamines and one-carbon metabolism

ABSTRACT: Aneuploidy, having an unbalanced genome, is an aberration commonly found in tumours but rare in normal tissues. It gives rise to proteotoxic stress as well as a stereotypical oxidative shift which makes these cells sensitive to internal and environmental stresses. Using Drosophila as a model, we investigated the changes in transcription in response to ongoing changes to ploidy (chromosomal instability, CIN). We noticed changes in genes affecting one-carbon metabolism, specifically those affecting the production and use of s-adenosyl methionine (SAM). Depletion of several of these genes led to cell death by apoptosis in CIN cells, but not normal proliferating cells. We found that CIN cells are particularly sensitive to SAM metabolism at least partly because of its role in generating polyamines. Feeding animals spermine was seen to rescue the cell death caused by loss of SAM synthase in CIN tissues. Loss of polyamines led to decreased rates of autophagy and sensitivity to reactive oxygen species (ROS), which we have shown contribute significantly to cell death in CIN cells. These findings suggest that a well-tolerated metabolic intervention like polyamine inhibition has the potential to target CIN tumours via a relatively well characterized mechanism.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE231601 | GEO | 2023/05/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Snapshot of translation in mammalian cells that are depleted of polyamines or replete with polyamines

Project description:Snapshot of translation in mammalian cells that are depleted of polyamines or replete with polyamines. Hek293T cells treated with DFMO or Spermidine.

2018-10-11 | GSE111517 | GEO

Snapshot of translation in mammalian cells that are depleted of polyamines or replete with polyamines

Project description:Snapshot of translation in mammalian cells that are depleted of polyamines or replete with polyamines

| PRJNA437287 | ENA

Proteomic alterations in early stage cervical cancer

Project description:Cervical cancer is characterized by a well-defined pre-malignant phase, cervical intraepithelial neoplasia (CIN). Identification of high grade CIN lesions by population-based screening programs and their subsequent treatment has led to a significant reduction of the incidence and mortality of cervical cancer. Cytology-based testing of cervical smears is the most widely used cervical cancer screening method, but is not ideal, as the sensitivity for detection of CIN2 and higher (CIN2+) is only ~55%. Therefore, more sensitive and specific biomarkers for cervical cancer and its precancerous stages are needed.

2018-05-03 | PXD008723 | Pride

Targeting polyamines catabolism to counteract the detrimental effects of cellular senescence

Project description:To investigate the effect of pharmacological targeting of polyamines catabolic enzymes in the establishment and reversion of the senescent phenotype

2022-10-18 | GSE212085 | GEO

Polyamines are critical for the induction of the glutamate decarboxylase-dependent acid resistance system in Escherichia coli

Project description:As part of our studies on the biological functions of polyamines we have used a mutant of Escherichia coli that lacks all the genes for polyamine biosynthesis for a global transcription analysis on the effect of added polyamines. The most striking early response to polyamine addition is the increased expression of the genes for the glutamate dependent acid resistance system (GDAR) that is essential for the survival of bacteria when passing through the acid environment of the stomach. Not only were the two genes for glutamate decarboxylases (gadA and gadB) and the gene for glutamate -γ-aminobutyrate antiporter (gadC) induced by polyamine addition, but also the various genes involved in the regulation of this system were induced. We confirmed the importance of polyamines for the induction of the GDAR system by direct measurement of glutamate decarboxylase activity and acid-survival. Effects of deletions of the regulatory genes in the GDAR system and on the effects of overproduction of two of these genes were also studied. Strikingly, overproductions of the alternate sigma factor rpoS and of the regulatory gene gadE resulted in very high levels of glutamate decarboxylase and almost complete protection against acid stress even in the absence of any polyamines. Thus, these data show that a major function of polyamines in E. coli is protection against acid stress by increasing the synthesis of glutamate decarboxylase, presumably by increasing the levels of the rpoS and gadE regulators. E. coli coltures were treated with PA and PS and its control with three biological replications

2013-12-05 | E-GEOD-49918 | biostudies-arrayexpress

Polyamines are critical for the induction of the glutamate decarboxylase-dependent acid resistance system in Escherichia coli

2013-12-05 | GSE49918 | GEO

Polyamines induce the glutamate decarboxylase acid response system by increasing the level of the σ38 subunit (RpoS) of Escherichia coli RNA polymerase via gadE regulon

Project description:To study the physiological roles of polyamines, we have carried out a global microarray analysis on the effect of adding polyamines to an Escherichia coli mutant that lacks polyamines because of deletions in the genes in the polyamine biosynthetic pathway. Previously, we have reported that the earliest response to the polyamine addition is the increased expression of the genes for the glutamate dependent acid resistance system (GDAR). We also presented preliminary evidence for the involvement of rpoS and gadE regulators. In the current study further confirmation of the regulatory roles of rpoS and gadE is shown by a comparison of genome-wide expression profiling data from a series of microarrays comparing the genes induced by polyamine addition to polyamine-free rpoS+/gadE+ cells with genes induced by polyamine addition to polyamine-free ∆rpoS and ∆gadE cells. The results indicate that most of the genes in the E. coli GDAR system that are induced by polyamines require rpoS and gadE. Our data also show that, gadE is the main regulator of GDAR and other acid-fitness-island genes. Both polyamines and rpoS are necessary for the expression of gadE genes from the three promoters of gadE (P1, P2 and P3). The most important effect of polyamine addition is the very rapid post-transcriptional increase in the level of RpoS sigma factor. Our current hypothesis is that polyamines increase the level of RpoS protein, and that this increased RpoS level is responsible for the stimulation of gadE expression, which in turn induces the GDAR system in E. coli. Three replications for E. coli strains HT874, HT873, HT875, HT873 treated with or no polyamines(PA)

2015-08-06 | E-GEOD-67119 | biostudies-arrayexpress

Polyamines induce the glutamate decarboxylase acid response system by increasing the level of the σ38 subunit (RpoS) of Escherichia coli RNA polymerase via gadE regulon

2015-08-06 | GSE67119 | GEO

Chromosome copy number changes in Mad2-null-driven p53 null HCC and T-ALL samples

Project description:Mad2 and p53 loss were combined in liver or T-cells specificely leading to early onset and highly aggressive aneuploid HCC and T-ALL. Tumours were characterized for (recurrrent) copy number changes with a focus on whole chromosome abnormalities. DNA content was compared to the DNA content of sex-matched uninfiltrated control liver samples from litter mates Chromosome instability (CIN) leads to aneuploidy and copy number variations (CNVs). Even though both are hallmarks of cancer cells, aneuploidy inhibits proliferation of untransformed cells, suggesting that cancer cells have adapted to cope with CIN. The spindle assembly checkpoint (SAC) prevents CIN by monitoring chromosome attachment and sister chromatid tension in mitosis. By conditionally inactivating Mad2, an essential SAC gene, we find that SAC inactivation in T-cells or hepatocytes is remarkably well tolerated and becomes tumorigenic when placed in a p53null or p53+/- predisposed background. The resulting T-ALLs and HCCs are highly aneuploid, exhibit clonal copy number changes that are tumor specific despite ongoing CIN, indicating that CIN is a powerful driver of tumor evolution.

2017-03-20 | GSE63686 | GEO

Single cell genome sequencing of murine and human tumors

Project description:Chromosome instability (CIN) leads to aneuploidy, a state in which cells have abnormal numbers of chromosomes affecting two out of three cancers. Continuous CIN in murine T-cells was previously shown to dramatically accelerate lymphomagenesis in a p53-deficient background. Despite the predicted ongoing CIN in our mouse model, we observed whole chromosome copy number changes that affected all lymphoma cells, suggesting that CIN is somehow suppressed in the aneuploid lymphomas or that selection for frequently lost/gained chromosomes outcompetes the CIN-imposed missegregation. To distinguish between these explanations and to examine karyotype dynamics in CIN lymphoma, we used a newly developed single-cell whole genome-sequencing (scWGS) platform that provides a complete and unbiased overview of copy number variations (CNV) in individual cells. In this study we applied single cell whole genome sequencing (scWGS) to map and quantify karyotype heterogeneity in primary mouse lymphoma and human leukaemia samples. We used cohorts of Mps1f/f; Lck-Cre+, Mps1f/f; p53f/f; Lck-Cre+ and Mps1f/f; p53f/+; Lck-Cre+ mice, and Lck-Cre- mice as controls. Mice were sacrificed when exhibiting signs of lymphoma (10-14 weeks of age, typically dyspnoea due to an enlarged thymus), thymuses were harvested, and primary T-ALL single cell suspensions were frozen for subsequent single cell sequencing analysis.

2016-04-16 | E-MTAB-4183 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data