Phosphoethanolamine Accumulation Protects Cancer Cells under Glutamine Starvation through Downregulation of PCYT2
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ABSTRACT:
PROVIDER: PRJNA561847 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10027927_1.fastq.gz | Fastqsanger.gz | |||
| SRR10027927_2.fastq.gz | Fastqsanger.gz | |||
| SRR10027928_1.fastq.gz | Fastqsanger.gz | |||
| SRR10027928_2.fastq.gz | Fastqsanger.gz | |||
| SRR10027929_1.fastq.gz | Fastqsanger.gz |
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Project description:The conditions of the tumor microenvironment, such as nutrient starvation, play critical roles in cancer progression. However, the role of glutamine deprivation in cancer progression is not studied as extensively as that of hypoxia. Here, we show that glutamine starvation triggered down-regulation of PCYT2 by stimulating accumulation of PEtn. Interestingly, glutamine upregulated series of glutamine-responsive genes, not only PCYT2. Furthermore, glutamine-responsive genes were associated with overall survival of cancer patients. Thus, our findings show that glutamine responsive genes such as PCYT2 are key for progression of cancer cells, partly protecting cancer cells to glutamine starvation.
2019-08-24 | GSE136289 | GEO
Project description:Phosphatidylethanolamine (PE) biosynthesis is critical for membrane biology and cellular homeostasis. However, its specific role in antiviral innate immunity remains poorly understood. Here, we demonstrate that inhibition of phosphoethanolamine cytidylyltransferase 2 (PCYT2), a key enzyme in PE biosynthesis, promotes TBK1 activation to enhance antiviral immune response. Mechanistically, PCYT2 deficiency leads to the accumulation of diacylglycerol (DAG), which activates protein kinase C δ (PKCδ). We identify PKCδ as a direct kinase for TBK1, and demonstrate that it binds to and phosphorylates TBK1 at Ser716. This Ser716 phosphorylation facilitates subsequent canonical phosphorylation at Ser172, resulting in hyperactivation of the TBK1–IRF3 axis. Our findings uncover a novel link between phospholipid metabolism and antiviral innate immunity, suggesting that targeting the PE biosynthesis pathway could be a potential therapeutic strategy against viral infections.
2026-05-07 | GSE324604 | GEO
Project description:Numerous mechanisms to support cells under conditions of transient nutrient starvation have been described. The tumor suppressor protein p53 can contribute to the adaptation of cells to metabolic stress through various mechanisms that may help cancer cell survival in nutrient limiting conditions. We show here that p53 helps cancer cells to survive glutamine starvation by promoting the expression of SLC1A3, an aspartate/glutamate transporter that allows the utilization of aspartate to support cells in the absence of extracellular glutamine. Under glutamine deprivation, SLC1A3 expression maintains electron transport chain and tricarboxylic acid cycle activity, promoting de novo glutamate, glutamine and nucleotide synthesis to rescue cell viability. Tumor cells with high levels of SLC1A3 expression are resistant to glutamine starvation and SLC1A3 depletion retards the growth of these cells in vitro and in vivo, suggesting a therapeutic potential for SLC1A3 inhibition.
2018-06-28 | GSE116087 | GEO
Project description:Glutamine addiction represents a metabolic vulnerability of cancer cells although effective therapeutic targeting of the pathways involved remains to be realized. Here, we disclose the critical role of IFRD1 (interferon-related developmental regulator 1) in the adaptive survival of hepatocellular carcinoma cells (HCC) during glutamine starvation. The induction and translocation of IFRD1 to the endoplasmic reticulum inhibits autophagy by promoting proteasomal degradation of the key autophagy regulator ATG14 in a TRIM21-dependent manner. On the contrary, enforced IFRD1 loss increases autophagy flux leading to cell death. This effect is largely realized through the autophagy-dependent degradation of histone H1.0 causing globally enhanced chromatin accessibility associated with unchecked increases in ribosome and protein biosynthesis . This in turn leads to metabolic exhaustion and death under glutamine starvation. Practically, IFRD1 depletion in preclinical HCC models potentiates glutamine limiting strategies including synergizing with the glutaminase-1 selective inhibitor CB-839. Thus, IFRD1 supports the adaptive survival of cancer cells under glutamine starvation, with potential as a therapeutic target in anti-cancer applications.
2024-03-23 | GSE217406 | GEO
Project description:Cellular senescence impacts many physiological and pathological processes. A durable cell cycle arrest, inflammatory secretory phenotype, and metabolic reprogramming characterize it. Identifying common and specific metabolic liabilities in senescence provide novel inroads to exploit senescence targeting for health benefits. Here, we use dynamic transcriptome and metabolome profiling in different senescence subtypes to reveal common and specific metabolic signatures. Specifically, we pinpoint the homeostatic switch of glycerol-3-phosphate (G3P) and phosphoethanolamine (PEtn) accumulation, intimately linking lipid metabolism to the senescence gene expression program. Mechanistically, p53-dependent glycerol kinase (GK) activation and post-translational inactivation of Phosphate Cytidylyltransferase 2- Ethanolamine (PCYT2) regulate this metabolic switch, which is senogenic. Conversely, G3P phosphatase (G3PP) and Ethanolamine-Phosphate Phospho-Lyase (ETNPPL)-based scavenging of G3P and PEtn is senomorphic. Collectively, our study ties the G3P-PEtn homeostatic switch to controlling lipid droplet biogenesis and phospholipid flux in senescent cells, providing a potential, novel therapeutic avenue for senescence targeting in pathophysiology.
2024-02-01 | GSE248823 | GEO
Project description:Cellular senescence impacts many physiological and pathological processes. A durable cell cycle arrest, inflammatory secretory phenotype, and metabolic reprogramming characterize it. Identifying common and specific metabolic liabilities in senescence provide novel inroads to exploit senescence targeting for health benefits. Here, we use dynamic transcriptome and metabolome profiling in different senescence subtypes to reveal common and specific metabolic signatures. Specifically, we pinpoint the homeostatic switch of glycerol-3-phosphate (G3P) and phosphoethanolamine (PEtn) accumulation, intimately linking lipid metabolism to the senescence gene expression program. Mechanistically, p53-dependent glycerol kinase (GK) activation and post-translational inactivation of Phosphate Cytidylyltransferase 2- Ethanolamine (PCYT2) regulate this metabolic switch, which is senogenic. Conversely, G3P phosphatase (G3PP) and Ethanolamine-Phosphate Phospho-Lyase (ETNPPL)-based scavenging of G3P and PEtn is senomorphic. Collectively, our study ties the G3P-PEtn homeostatic switch to controlling lipid droplet biogenesis and phospholipid flux in senescent cells, providing a potential, novel therapeutic avenue for senescence targeting in pathophysiology.
2024-02-01 | GSE248822 | GEO
Project description:Corynebacterium glutamicum, a gram-positive soil bacterium used for the industrial production of amino acids such as L-glutamate and L-lysine, is able to use a number of different nitrogen sources, such as ammonium, urea, or creatinine. In this communication, we show that L-glutamine serves as an excellent nitrogen source for C. glutamicum and allows similar growth rates in glucose minimal medium as ammonium. A transcriptome comparison revealed a strong induction of the nitrogen starvation response when glutamine was used as nitrogen source. Subsequent growth experiments with a variety of mutants defective in nitrogen metabolism showed that glutamate synthase is crucial for glutamine utilization, while a putative glutaminase is dispensable under the experimental conditions used. The fact that the glutamate synthase encoding gltBD operon is under strict nitrogen control explains the necessity for induction of the nitrogen starvation response. The paradox situation that the nitrogen starvation response is induced although intracellular L-glutamine levels are high has implications on nitrogen sensing. In contrast to other gram-positive and gram-negative bacteria such as Bacillus subtilis, Salmonella typhimurium, and Klebsiella pneumoniae, a drop in glutamine concentration obviously does not serve as a nitrogen starvation signal in C. glutamicum.
2010-10-05 | GSE19779 | GEO
Project description:Corynebacterium glutamicum, a gram-positive soil bacterium used for the industrial production of amino acids such as L-glutamate and L-lysine, is able to use a number of different nitrogen sources, such as ammonium, urea, or creatinine. In this communication, we show that L-glutamine serves as an excellent nitrogen source for C. glutamicum and allows similar growth rates in glucose minimal medium as ammonium. A transcriptome comparison revealed a strong induction of the nitrogen starvation response when glutamine was used as nitrogen source. Subsequent growth experiments with a variety of mutants defective in nitrogen metabolism showed that glutamate synthase is crucial for glutamine utilization, while a putative glutaminase is dispensable under the experimental conditions used. The fact that the glutamate synthase encoding gltBD operon is under strict nitrogen control explains the necessity for induction of the nitrogen starvation response. The paradox situation that the nitrogen starvation response is induced although intracellular L-glutamine levels are high has implications on nitrogen sensing. In contrast to other gram-positive and gram-negative bacteria such as Bacillus subtilis, Salmonella typhimurium, and Klebsiella pneumoniae, a drop in glutamine concentration obviously does not serve as a nitrogen starvation signal in C. glutamicum. Three biological replicates were performed. To analyse how L-glutamine influences global gene expression when used as sole nitrogen source instead of ammonium, DNA microarray analyses were performed. For this purpose RNA was isolated from exponentially growing cells cultivated in CgXII medium containing glucose as carbon source and either L-glutamine or ammonium sulphate as nitrogen source.
2010-10-05 | E-GEOD-19779 | biostudies-arrayexpress
Project description:<p>Cellular senescence affects many physiological and pathological processes and is characterized by durable cell cycle arrest, an inflammatory secretory phenotype and metabolic reprogramming. Here, by using dynamic transcriptome and metabolome profiling in human fibroblasts with different subtypes of senescence, we show that a homeostatic switch which results in glycerol-3-phosphate (G3P) and phosphoethanolamine (PEtn) accumulation links lipid metabolism to the senescence gene expression program. Mechanistically, p53-dependent glycerol kinase (GK) activation and post-translational inactivation of Phosphate Cytidylyltransferase 2-Ethanolamine (PCYT2) regulate this metabolic switch, which promotes triglyceride accumulation in lipid droplets and induces the senescence gene expression program. Conversely, G3P phosphatase (G3PP) and Ethanolamine-Phosphate Phospho-Lyase (ETNPPL)-based scavenging of G3P and PEtn acts in a senomorphic way by reducing G3P and PEtn accumulation. Collectively, our study ties G3P and PEtn accumulation to controlling lipid droplet biogenesis and phospholipid flux in senescent cells, providing a potential therapeutic avenue for targeting senescence and related pathophysiology.</p>
2024-01-09 | MTBLS7118 | MetaboLights
Project description:Glutamine recovers stress granules after cellular starvation to help mount cancer stress response
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