Metabolic profiling of prostate cancer in skeletal microenvironments identifies G6PD as a key mediator of growth and survival
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA788945 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17230988_1.fastq.gz | Fastqsanger.gz | |||
| SRR17230988_2.fastq.gz | Fastqsanger.gz | |||
| SRR17230989_1.fastq.gz | Fastqsanger.gz | |||
| SRR17230989_2.fastq.gz | Fastqsanger.gz | |||
| SRR17230990_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:The spread of cancer to bone is invariably fatal, with complex crosstalk between tumour cells and the bone microenvironment responsible for driving disease progression. By combining in silico analysis of patient datasets with metabolomic profiling of prostate cancer cells cultured with bone cells, we demonstrate the changing energy requirements of prostate cancer cells in the bone microenvironment, identifying the pentose phosphate pathway (PPP) as elevated in prostate cancer bone metastasis, with increased expression of the PPP rate-limiting enzyme (G6PD) associated with a reduction in progression-free survival. Genetic and pharmacologic manipulation demonstrates that G6PD inhibition reduces prostate cancer growth and migration, associated with changes in cellular redox state and increased chemosensitivity. Genetic blockade of G6PD in vivo results in reduction of tumour growth within bone. In summary, we demonstrate the metabolic plasticity of prostate cancer cells in the bone microenvironment, identifying the PPP and G6PD as metabolic targets for the treatment of prostate cancer bone metastasis.
2022-02-25 | GSE190928 | GEO
Project description:The spread of cancer to bone is invariably fatal, with complex cross-talk between tumor cells and the bone microenvironment responsible for driving disease progression. By combining in silico analysis of patient datasets with metabolomic profiling of prostate cancer cells cultured with bone cells, we demonstrate the changing energy requirements of prostate cancer cells in the bone microenvironment, identifying the pentose phosphate pathway (PPP) as elevated in prostate cancer bone metastasis, with increased expression of the PPP rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD) associated with a reduction in progression-free survival. Genetic and pharmacologic manipulation demonstrates that G6PD inhibition reduces prostate cancer growth and migration, associated with changes in cellular redox state and increased chemosensitivity. Genetic blockade of G6PD in vivo results in reduction of tumor growth within bone. In summary, we demonstrate the metabolic plasticity of prostate cancer cells in the bone microenvironment, identifying the PPP and G6PD as metabolic targets for the treatment of prostate cancer bone metastasis.
| S-EPMC8880772 | biostudies-literature
Project description:Site-specifically acetylated G6PD expressed in bacteria or cultured mammalian cells by genetically encoding the incorporation of acetylated lysine. Purified G6PD (expressed in E. coli) or immunopurified G6PD (expressed in HEK293T cells) were subjected to LC-MS/MS analysis.
2023-10-24 | PXD044906 | Pride
Project description:To identify acetylation-dependent posttranslational modifications (PTMs) of G6PD, site-specifically acetylated and Flag-tagged G6PD was expressed in HEK293T cells by genetically encoding the incorporation of acetylated lysine in response to an in-frame TAG stop codon. K403-acetylated G6PD (sample) and K414-acetylated G6PD (control) were co-expressed with WT Fyn kinase and a catalytically inactive mutant of Fyn (FynDN). G6PD was immunoprecipitated using anti-Flag beads before MS analysis.
2023-10-24 | PXD041775 | Pride
Project description:Our findings establish NIK as a pivotal regulator of T cell metabolism in anti-tumor immunity and highlight a posttranslational mechanism of metabolic regulation involving the G6PD-NADPH redox system. CoIP assays revealed a strong physical interaction between NIK and G6PD in both T cells and transiently transfected 293 cells, suggesting G6PD to be a direct target of NIK. Using a phosphoprotein gel analysis approach, we demonstrated that NIK expression stimulated G6PD phosphorylation. To further study the mechanism, we performed mass spectrometry identify phosphorylation sites of G6PD stimulated by NIK
2020-10-05 | PXD020943 | Pride
Project description:Cancer cells heavily rely on nicotinamide adenine dinucleotide phosphate (NADPH) to counteract oxidative stress and facilitate reductive biosynthesis. One crucial route for NADPH production operates through the oxidative pentose phosphate pathway, with a pivotal step at glucose-6-phosphate dehydrogenase (G6PD). This study delves into the repercussions of G6PD ablation on the development of lung tumors driven by the KRAS oncogene and deficient in LKB1 (KL). The research involved comparing the growth of KL lung tumors with or without G6PD, revealing a significant inhibition of KL lung tumor growth upon G6PD loss. Subsequently, RNA-seq analysis was employed to identify the alterations in gene expression following G6PD deletion, providing insights into the underlying mechanisms.
2024-01-23 | GSE253613 | GEO
Project description:Neurofibromatosis Type II is a genetic condition caused by loss of the NF2 gene, resulting in activation of the YAP/TAZ pathway and recurrent growth of benign tumors from Schwann cells, the glia of the peripheral nervous system. Unfortunately, no pharmacological therapy is currently available for NFII. Here, we undertake a genome-wide CRISPR/cas9 screen to search for synthetic-lethal genes that, when inhibited, cause death of NF2 mutant cells but not NF2 wildtype cells. We thereby identify ACSL3 and G6PD as two synthetic-lethal partners for NF2. We find that NF2 mutant Schwann cells are vulnerable to G6PD inhibition because they have low levels of ME1. G6PD and ME1 redundantly generate cytosolic NADPH needed by cells to fight oxidative stress. Lack of either one of the two is compatible with cell viability, but down-regulation of both leads to Schwann cell death. Since genetic deficiency for G6PD is tolerated in the human population, this raises the possibility that G6PD could be a pharmacological target for NFII.
2024-04-24 | GSE219136 | GEO
Project description:Neurofibromatosis Type II is a genetic condition caused by loss of the NF2 gene, resulting in activation of the YAP/TAZ pathway and recurrent growth of benign tumors from Schwann cells, the glia of the peripheral nervous system. Unfortunately, no pharmacological therapy is currently available for NFII. Here, we undertake a genome-wide CRISPR/cas9 screen to search for synthetic-lethal genes that, when inhibited, cause death of NF2 mutant cells but not NF2 wildtype cells. We thereby identify ACSL3 and G6PD as two synthetic-lethal partners for NF2. We find that NF2 mutant Schwann cells are vulnerable to G6PD inhibition because they have low levels of ME1. G6PD and ME1 redundantly generate cytosolic NADPH needed by cells to fight oxidative stress. Lack of either one of the two is compatible with cell viability, but down-regulation of both leads to Schwann cell death. Since genetic deficiency for G6PD is tolerated in the human population, this raises the possibility that G6PD could be a pharmacological target for NFII.
2024-04-24 | GSE219135 | GEO
Project description:Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma, has a high degree of clinical and biological heterogeneity. Although most patients can be cured with R-CHOP immunochemotherapy,30-40% of patients have progression or recurrence after treatment. Therefore, there is an urgent need to find new treatments to improve the survival rate of this group of patients. Natural small molecule drugs have unique advantages as anticancer agents due to their low toxicity and multiple targets. This project aims to explore potentially effective natural compounds as new therapeutic strategies for DLBCL. We found that Cinobufagin is a potentially effective therapeutic agent for DLBCL. Glucose 6 phosphate dehydrogenase (G6PD), a risk factor for poor prognosis in DLBCL, was a direct target of Cinobufagin. By inhibiting the enzyme activity of G6PD, Cinobufagin could inhibit DNA synthesis and the production of reductive NADPH, thereby inducing ROS accumulation and apoptosis of DLBCL cells. Our findings provide new strategies for the treatment of DLBCL.
2024-07-31 | GSE254385 | GEO
Project description:In order to analyze the changes of G6PD enzyme activity regulating the metabolism and proliferation pathways in HCC cell. After G6PD enzyme activity inhibitor RRx-1 treated with 20μM concentrations for 24h in Huh7 cell. Differential expression of genes were selected after RNA sequencing. Then David Bioinformatics was utilized to identify the most significantly regulated GOTERMs and KEGG pathways based on the transcriptional changes.
2020-11-12 | E-MTAB-9712 | biostudies-arrayexpress