Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Role of copper in progression of clear cell renal cell carcinoma [Spatial transcriptomics]

ABSTRACT: Copper (Cu) is an essential trace element required for mitochondrial respiration. We show that Cu drives coordinated metabolic remodeling of bioenergy, biosynthesis and redox homeostasis and promotes tumor growth and progression of clear cell renal cell carcinoma (ccRCC). Late-stage ccRCCs accumulate Cu and allocate it to cytochrome c oxidase stimulating bioenergy production. Cu induces TCA cycle-dependent oxidation of glucose and its utilization for biosynthesis of a glutathione pool that protects against H2O2 generated during mitochondrial respiration, therefore coordinating bioenergy production with redox protection. Single cell transcriptomics determined induction of mitochondrial electron transport chain, expression of NRF2 targets and glutathione biosynthesis, and decrease in HIF activity, the hallmark of ccRCC, during disease progression. Spatial transcriptomics identified that cancer cells with proliferative phenotype are embedded in clusters of cells with oxidative metabolism supporting effects of metabolic states on ccRCC progression. Our work establishes novel vulnerabilities with potential for therapeutic interventions in ccRCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE250163 | GEO | 2024/10/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Role of copper in progression of clear cell renal cell carcinoma [RNA-seq]

Project description:Copper (Cu) is an essential trace element required for mitochondrial respiration. We show that Cu drives coordinated metabolic remodeling of bioenergy, biosynthesis and redox homeostasis and progression of clear cell renal cell carcinoma (ccRCC). Cu stimulates tumor growth. Late-stage ccRCCs accumulate Cu and allocate it to cytochrome c oxidase stimulating bioenergy production. Cu induces TCA cycle-dependent oxidation of glucose and its utilization for biosynthesis of a glutathione pool that protects against H2O2 generated during mitochondrial respiration, therefore coordinating bioenergy production with redox protection.

2024-10-18 | GSE250028 | GEO

Manipulating mitochondrial reactive oxygen species alters survival in unexpected ways in a Drosophila Cdk5 model of neurodegeneration

Project description:Reactive oxygen species (ROS) are associated with aging and neurodegeneration, but the significance of this association remains obscure. Here, using a Drosophila Cdk5 model of age-related neurodegeneration, we probe this relationship in the pathologically relevant tissue, the brain, by quantifying three specific mitochondrial ROS and manipulating these redox species pharmacologically. Our goal is to ask whether pathology-associated changes in redox state are detrimental for survival, whether they may be beneficial responses to pathology, or whether they are simply covariates of pathology that do not alter viability. We find, surprisingly, that increasing mitochondrial H2O2 correlates with improved survival. We also find evidence that drugs that alter the mitochondrial glutathione redox potential modulate survival primarily through the compensatory effects they induce rather than through their direct effects on the final mitochondrial glutathione redox potential per se. We also find that the response to treatment with a redox-altering drug varies dramatically depending on the age at which the drug is administered, the duration of the treatment, and the genotype of the individual receiving the drug. These data have important implications for the design and interpretation of studies investigating the effect of redox state on health and disease as well as on efforts to modify the redox state to achieve therapeutic goals.

2024-08-22 | GSE274587 | GEO

Mitochondrial complex I promotes kidney cancer metastasis

Project description:Most kidney cancers display metabolic dysfunction but how this relates to cancer progression in humans is unknown. We infused 13C-labeled nutrients during surgical tumour resection in over 80 patients with kidney cancer. Labeling from [U-13C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all metabolic reprogramming in these tumours. Compared to the adjacent kidney, clear cell renal cell carcinomas (ccRCC) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in organotypic cultures ex vivo, indicating that suppressed labeling is tissue intrinsic. Infusions of [1,2-13C]acetate and [U-13C]glutamine in patients, coupled with measurements of respiration in mitochondria isolated from kidneys and tumours, reveal electron transport chain (ETC) defects in ccRCC. However, ccRCC metastases unexpectedly have enhanced TCA cycle labeling compared to primary ccRCCs, indicating a divergent metabolic program during metastasis in patients. In mice, stimulating respiration or NADH recycling in kidney cancer cells is sufficient to promote metastasis, while inhibiting ETC complex I decreases metastasis. These findings indicate that metabolic properties and liabilities evolve during kidney cancer progression in humans, and that mitochondrial function is limiting for metastasis but not for growth at the original site.

2024-06-17 | GSE251905 | GEO

Transcriptomic characterization of spl7 and Col-0 ecotypes of Arabidopsis reveals new aspects of Fe-Cu crosstalk

Project description:Iron (Fe) and copper (Cu) are essential metal micronutrients that are necessary for many redox reactions. The uptake of these metals is tightly regulated in plants. Some redox processes can alternatively use Fe-containing proteins or Cu-containing proteins, depending on nutritional status. Copper deficiency can rescue a Cucumis melo Fe uptake deficient mutant, and Fe deficiency can result in increased accumulation of Cu. However, the system responsible for Fe-deficiency-regulated Cu-uptake is unknown. To understand the genes and gene networks associated with Fe-deficiency regulated Cu uptake and Fe-Cu cross-talk, we conducted transcriptomic profiling of roots and rosettes of spl7 (a Cu uptake deficient mutant in arabidopsis) and Col-0 (WT) grown under Fe, Cu and simultaneous Fe and Cu deficiency conditions.

2018-03-01 | GSE104916 | GEO

Transcriptomic analysis by array of reactivation of dihydroorotate dehydrogenase by respiration restores tumor growth of mitochondrial DNA-depleted cancer cells.

Project description:Tumor cells without mitochondrial DNA (mtDNA) reconstitute oxidative phosphorylation (OXPHOS) by acquiring host mitochondria from stromal cells, but the reasons why functional respiration is crucial for tumorigenesis remain unclear. To address this issue, we used time-resolved analysis of the initial stages of tumor formation by cells devoid of mtDNA and genetic manipulations of components of OXPHOS. We show that pyrimidine biosynthesis, supported by respiration-linked dihydroorotate dehydrogenase (DHODH), is strictly required to overcome cell cycle arrest, while mitochondrial ATP generation is dispensable for tumorigenesis.

2018-10-01 | E-MTAB-6150 | biostudies-arrayexpress

Glycolytic preconditioning in astrocytes mitigates trauma-induced neurodegeneration

Project description:Reducing mitochondrial electron transport induces a Warburg-like shift to accommodate for the energetic burden caused by brain trauma without overwhelming mitochondrial cellular respiration and cellular redox to salvage dopaminergic neurons. This metabolic shift is evident in the transcriptional upregulation of key genes in the Pyruvate Dehydrogenase Complex and glycolytic pathway.

2021-08-26 | GSE179905 | GEO

A bioenergetic shift is required for spermatogonial differentiation

Project description:A bioenergetic balance between glycolysis and mitochondrial respiration is particularly important for stem cell fate specification. It however remains to be determined whether undifferentiated spermatogonia switch their preference of bioenergy production during differentiation. In this study, we found that ATP generation in spermatogonia was gradually increased upon retinoic acid-induced differentiation. To accommodate this elevated energy demand, retinoic acid signaling concomitantly switched ATP production in spermatogonia from glycolysis to mitochondrial respiration, accompanied by increased levels of reactive oxygen species. In addition, inhibition of glucose conversion to glucose-6-phosphate or pentose phosphate pathway blocked the formation of c-Kit+ differentiating germ cells, suggesting that metabolites produced from glycolysis are required for spermatogonial differentiation. We further demonstrated that the expression levels of several metabolic regulators and enzymes were significantly altered upon retinoic acid-induced differentiation by both RNA-seq analyses and quantitative proteomics. Taken together, our data unveil a critically regulated bioenergetic balance between glycolysis and mitochondrial respiration which is required for spermatogonial proliferation and differentiation.

2021-09-09 | PXD019136 | Pride

1.0 mM As(III) stressed yap1 deletion mutant vs 1.0 mM As(III) stressed wild-type after 1 hour

Project description:volved enabling cells to evade toxicity and acquire tolerance. Herein, we explored how Saccharomyces cerevisiae (budding yeast) respond to trivalent arsenic (arsenite) by quantitative and kinetic transcriptome, proteome and sulfur metabolite profiling. Arsenite exposure affected transcription of genes encoding functions related to protein biosynthesis, arsenic detoxification, oxidative stress defense, redox maintenance and proteolytic activity. Importantly, enzymes involved in sulfate assimilation and glutathione biosynthesis were induced at both gene and protein levels. Kinetic metabolic profiling evidenced a significant increase in the pools of sulfur metabolites as well as elevated glutathione levels. Moreover, the flux in the sulfur assimilation pathway as well as the glutathione synthesis rate strongly increased with a concomitant reduction of sulfur incorporation into proteins. By combining comparative genomics and molecular analyses, we pin-pointed transcription factors that mediate thecore of the transcriptional response to arsenite. Taken together, our data reveals that arsenite-exposed cells channel a large part of assimilated sulfur into glutathione biosynthesis and we provide evidence that the transcriptional regulators Yap1p and Met4p control this response in concert. Keywords: stress

2007-10-18 | GSE6071 | GEO

0.2 mM As(III) stressed met4 deletion mutant vs 0.2 mM As(III) stressed wild-type after 1 hour

Project description:Arsenic is ubiquitously present in nature and various mechanisms have evolved enabling cells to evade toxicity and acquire tolerance. Herein, we explored how Saccharomyces cerevisiae (budding yeast) respond to trivalent arsenic (arsenite) by quantitative and kinetic transcriptome, proteome and sulfur metabolite profiling. Arsenite exposure affected transcription of genes encoding functions related to protein biosynthesis, arsenic detoxification, oxidative stress defense, redox maintenance and proteolytic activity. Importantly, enzymes involved in sulfate assimilation and glutathione biosynthesis were induced at both gene and protein levels. Kinetic metabolic profiling evidenced a significant increase in the pools of sulfur metabolites as well as elevated glutathione levels. Moreover, the flux in the sulfur assimilation pathway as well as the glutathione synthesis rate strongly increased with a concomitant reduction of sulfur incorporation into proteins. By combining comparative genomics and molecular analyses, we pin-pointed transcription factors that mediate thecore of the transcriptional response to arsenite. Taken together, our data reveals that arsenite-exposed cells channel a large part of assimilated sulfur into glutathione biosynthesis and we provide evidence that the transcriptional regulators Yap1p and Met4p control this response in concert. Keywords: stress

2007-10-18 | GSE6072 | GEO

1.0 mM As(III) stressed wild-type vs (non-stressed) wild-type after 1 hour

2007-10-18 | GSE6066 | GEO