Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1069995 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27799462_1.fastq.gz | Fastqsanger.gz | |||
| SRR27799462_2.fastq.gz | Fastqsanger.gz | |||
| SRR27799463.fastq.gz | Fastqsanger.gz | |||
| SRR27799463_1.fastq.gz | Fastqsanger.gz | |||
| SRR27799463_2.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Solute carrier family 7 member 11 (SLC7A11; also known as xCT) is a cystine transporter frequently overexpressed in cancers. Cancer cells with high expression of SLC7A11 (SLC7A11high) are resistant to ferroptosis but exquisitely sensitive to glucose deprivation-induced cell death, although the underlying mechanism of the latter cell death remains poorly understood. Here we show that
We found that glucose deprivation induced a novel type of cell death in SLC7A11high cancer cells that was different from apoptosis or ferroptosis. And the bioorthogonal chemical proteomics analysis revealed that a large amount of actin cytoskeleton proteins were shown with significantly dysregulated disulfides induced by glucose starvation in SLC7A11high cancer cells. In mechanism, SLC7A11high mediated cystine uptake and subsequent reduction to cysteine forced disulfide stress on actin cytoskeleton upon glucose deprivation through draining intracellular reduced nicotinamide adenine dinucleotide phosphate (NADPH) pool, which was independent of generating reactive oxygen species (ROS). The disulfide stress on the actin cytoskeleton induced rapidly contracted actin filaments and detached from the plasma membrane, which incurred cell death. In the end, using whole-genome CRISPR/Cas9 knock-out screening we identified NCKAP1 as a downstream factor of SLC7A11 to promoting cell death upon glucose deprivation by inhibiting branched actin filaments.
| MSV000088066 | MassIVE
Project description:Increased utilization of glucose is a hallmark of cancer. Several studies are investigating the efficacy of glucose restriction on solid cancers, by glucose transporter blocking or glycolysis inhibition. However, the adaptations of cancer cells to glucose restriction are not known. Here, we report the discovery that glucose restriction in lung adenocarcinoma (LUAD) cells induces de-differentiation, leading to a more aggressive phenotype. Glucose deprivation causes a reduction in alpha-ketoglutarate (aKG), leading to attenuated activity of aKG-dependent histone demethylases and consequent histone hypermethylation. We further show that this de-differentiated and aggressive phenotype depends on unbalanced EZH2 activity, causing inhibition of prolyl-hydroxylase PHD3 and increased expression of hypoxia inducible factor 1a (HIF1a). Finally, we identified an HIF1a-dependent transcriptional signature with prognostic significance in human LUAD. Our studies further our knowledge of the relationship between glucose metabolism and cell differentiation in cancer, characterizing the epigenetic adaptation of cancer cells to glucose deprivation and identifying novel targets to prevent the development of resistance to metabolic therapies targeting glucose uptake and glycolysis.
2023-04-12 | E-MTAB-11678 | biostudies-arrayexpress
Project description:Cancer cells consume large amounts of glucose because of their specific metabolic pathway. However, cancer cells exist in tumor tissue where glucose is insufficient. To survive, cancer cells likely have the mechanism to elude their glucose addiction. Here we show that functional mitochondria are essential if cancer cells are to avoid glucose addiction. Cancer cells with dysfunctional mitochondria, such as mitochondrial DNA-deficient rho0 cells and electron transport chain blocker-treated cells, were highly sensitive to glucose deprivation. Our data demonstrated that this sensitization was caused by failure of the unfolded protein response (UPR), an adaptive response mediated by the endoplasmic reticulum (ER). This study suggests a link between mitochondria and the ER during the UPR under glucose deprivation conditions and that mitochondria govern cell fate, not only through ATP production and apoptosis regulation but also through modulating the UPR for cell survival.
2010-05-14 | GSE16157 | GEO
Project description:Cancer cells consume large amounts of glucose because of their specific metabolic pathway. However, cancer cells exist in tumor tissue where glucose is insufficient. To survive, cancer cells likely have the mechanism to elude their glucose addiction. Here we show that functional mitochondria are essential if cancer cells are to avoid glucose addiction. Cancer cells with dysfunctional mitochondria, such as mitochondrial DNA-deficient rho0 cells and electron transport chain blocker-treated cells, were highly sensitive to glucose deprivation. Our data demonstrated that this sensitization was caused by failure of the unfolded protein response (UPR), an adaptive response mediated by the endoplasmic reticulum (ER). This study suggests a link between mitochondria and the ER during the UPR under glucose deprivation conditions and that mitochondria govern cell fate, not only through ATP production and apoptosis regulation but also through modulating the UPR for cell survival. Human cancer cell lines (HT-1080, HT-29, and mtDNA-deficient cells derived from these cell lines) were selected for RNA extraction and hybridization on Affymetrix microarrays. We examined the unfolded protein response (UPR), an adaptive response mediated by the endoplasmic reticulum (ER), of cancer cells under stress conditions. Abbreviations List: AA, antimycin A; Bu, buformin; Met, metformin; Phen, phenformin; Rot, rotenone; VST, versipelostatin; TM, tunicamycin; 2DG, 2-deoxyglucose; GS, glucose starvation. Capital S (_S) indicates the supernatant of sample including floating cells.
2010-05-28 | E-GEOD-16157 | biostudies-arrayexpress
Project description:This microarray experiment was designed to identify genes and pathways modulated in glucose deprivation resistant (GDR) and glucose deprivation sensitive (GDS) clones of ovarian cancer xenografts. Tumors were established in NOD/SCID mice by s.c. injection of human ovarian cancer cells (IGROV-1 and SKOV3). After sacrifice GDR and GDS clones were obtained from ex vivo cultures of tumors. Once isolated, GDR and GDS clones were cultivated in normal-glucose (0h) or low-glucose condition (6 h and 24 h). Two different time points were selected to investigate both early (6 h) and late (24 h) transcriptional effects of glucose deprivation in IGROV-1 and SKOV3-derived clones. Total RNA was extracted from samples and hybridized on Affymetrix GeneChip™ PrimeView™ Human Gene Expression Arrays. Based on assessment of RNA quality and on quality control analyses (including MAplots and boxplots), only one sample, corresponding to GDR condition at 6 h of glucose deprivation in SKOV3 model, was excluded because it was deemed not suitable for data analysis. In order to evaluate the effects of glucose deprivation in the two models, expression data of IGROV-1 and SKOV3-derived GDR and GDS clones were normalized and analyzed separately. Raw microarray data and pre-processed data matrices are available together with the applied protocols. Results of differential expression analysis are provided as supplementary tables of the associated publication.
2023-05-31 | E-MTAB-12150 | biostudies-arrayexpress
Project description:Lung cancer is the most frequent cancer-related cause of death, and adenocarcinoma (LUAD) is the most frequent type. Despite the recent success of immunotherapies, survival of lung cancer patients has not significantly improved in the last decades. New therapies are necessary. We have previously identified sodium-glucose transporter 2 (SGLT2) as the major responsible for glucose uptake in LUAD, and we have showed that treatment with SGLT2 inhibitors significantly delays LUAD development and prolongs survival in murine models. However, our data shows that SGLT2 inhibitors also induce de-differentiation of LUAD cells, leading to a more aggressive phenotype and increased resistance to cisplatin. Glucose deprivation causes reduced αKG levels, leading to reduced activity of αKG-dependent histone demethylases and consequent histone hypermethylation. Supplementation of αKG or inhibition of the histone methyltransferase EZH2 reverse this phenotype, suggesting that this de-differentiated phenotype depends on insufficiency of αKG-dependent histone demethylases and unbalanced EZH2 activity. Consistently, double treatment with an SGLT2 inhibitor and an EZH2 inhibitor significantly reduces the tumor burden in a genetically engineered murine model of LUAD. We further characterized the effect of low glucose-induced tumor de-differentiation, identifying stabilization of hypoxia inducible factor 1α (HIF1α) as a major pathway responsible for the acquisition of a more aggressive phenotype following glucose deprivation. Finally, we identified an HIF1α-dependent transcriptional signature with prognostic significance in human LUAD. Our studies further our knowledge of the relationship between glucose metabolism and cell differentiation in cancer, characterizing the epigenetic adaptation of cancer cells to nutrient deprivation and identifying novel targets to prevent the development of resistance to metabolic therapies.
2022-12-31 | E-MTAB-11253 | biostudies-arrayexpress
Project description:Interventions: DM group and non-DM:Androgen Deprivation Therapy
Primary outcome(s): blood glucose, glycated hemoglobin, insulin;intestinal flora;fecal metabolites
Study Design: Factorial
| 2692103 | ecrin-mdr-crc
Project description:Glucose deprivation induced gene expression
| PRJNA668528 | ENA
Project description:Analysis of Hepatocellular carcinoma (HCC) cell line - Huh7 deprived of glucose. Glucose restriction promotes a liver tumor-initating cell phenotype. Results provide insight into the molecular mechanism of glucose deprivation in HCC.
2024-06-17 | GSE152927 | GEO
Project description:<h4>Background</h4>Cancer metabolism is emerging as an important focus area in cancer research. However, the in vitro cell culture conditions under which much cellular metabolism research is performed differ drastically from in vivo tumor conditions, which are characterized by variations in the levels of oxygen, nutrients like glucose, and other molecules like chemotherapeutics. Moreover, it is important to know how the diverse cell types in a tumor, including cancer stem cells that are believed to be a major cause of cancer recurrence, respond to these variations. Here, in vitro environmental perturbations designed to mimic different aspects of the in vivo environment were used to characterize how an ovarian cancer cell line and its derived, isogenic cancer stem cells metabolically respond to environmental cues.<h4>Results</h4>Mass spectrometry was used to profile metabolite levels in response to in vitro environmental perturbations. Docetaxel, the chemotherapeutic used for this experiment, caused significant metabolic changes in amino acid and carbohydrate metabolism in ovarian cancer cells, but had virtually no metabolic effect on isogenic ovarian cancer stem cells. Glucose deprivation, hypoxia, and the combination thereof altered ovarian cancer cell and cancer stem cell metabolism to varying extents for the two cell types. Hypoxia had a much larger effect on ovarian cancer cell metabolism, while glucose deprivation had a greater effect on ovarian cancer stem cell metabolism. Core metabolites and pathways affected by these perturbations were identified, along with pathways that were unique to cell types or perturbations.<h4>Conclusions</h4>The metabolic responses of an ovarian cancer cell line and its derived isogenic cancer stem cells differ greatly under most conditions, suggesting that these two cell types may behave quite differently in an in vivo tumor microenvironment. While cancer metabolism and cancer stem cells are each promising potential therapeutic targets, such varied behaviors in vivo would need to be considered in the design and early testing of such treatments.
2021-11-05 | MTBLS150 | MetaboLights