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Low cytosolic folate cycling is a hallmark of U251 glioblastoma cells reprogramming towards pluripotency [methylation]

ABSTRACT: Low cytosolic folate cycling is a hallmark of U251 glioblastoma cells reprogramming towards pluripotency [methylation]

PROVIDER: PRJNA482423 | ENA |

REPOSITORIES: ENA

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Low cytosolic folate cycling is a hallmark of U251 glioblastoma cells reprogramming towards pluripotency [RNA-seq]

Project description:we report that U251 glioblastoma tumor spheres exhibit low cytosolic folate cycle and a reprogrammmed mitochondrial folate cycle that is presumably oriented towards oxidizing the formyl group to CO2 with the production of TetraHydroFolate and release of NADPH instead of synthesizing formate

2019-07-01 | GSE117543 | GEO

Low cytosolic folate cycling is a hallmark of U251 glioblastoma cells reprogramming towards pluripotency [methylation]

Project description:What is known is that methionine-dependency is a feature of some cancers. So far, it was attributed to mutations in genes involved in the methionine de novo or salvage pathways. What is new is that in this work we propose that methionine dependency stems from an altered cellular metabolism. We provide evidence that in U251 glioblastoma cell line, only cancer stem cells -isolated as tumor spheres in non adherent conditions- are methionine dependent and not monolayer cells grown in adherent conditions. Transcriptome wide-sequencing reveals that several genes involved in cytosolic folate cycle are downregulated whereas some transcripts of genes involved in mitochondrial folate cycle are upregulated. Genome wide DNA methylation does not account for these changes in gene expression. Mass spectrometry measurements confirm that tumor spheres display low cytosolic folate cycle unable to produce enough 5-methyltetrahydrofolate to remethylate homocystein to methionine. This decreased 5-methyltetrahydrofolate bioavailability is presumably due to a reprogrammed mitochondrial folate cycle which instead of synthesizing formate, intended to fuel the cytosolic folate cycle, oxidizes the formyl group to CO2 with the attendant reduction of NADP+ to NADPH and release of tetrahydrofolate. The originality of this work resides in that it replaces methionine deprivation as a useful nutritional strategy in cancer growth control since cancer stem cells are much more tumoregenic than their non stem-like counterparts. Second, it reveals that the primary default responsible of the reprogrammation of folate metabolism originates in the mitochondria. Thus, mitochondrial enzymes could be novel and more promising anticancer targets than dihydrofolate reductase (DHFR), the current target of drug therapy linked with folate metabolism.

2019-07-01 | GSE117448 | GEO

Low cytosolic folate cycling is a hallmark of U251 glioblastoma cells reprogramming towards pluripotency

Project description:Low cytosolic folate cycling is a hallmark of U251 glioblastoma cells reprogramming towards pluripotency

| PRJNA482425 | ENA

Low cytosolic folate cycling is a hallmark of U251 glioblastoma cells reprogramming towards pluripotency [RNA-seq]

Project description:Low cytosolic folate cycling is a hallmark of U251 glioblastoma cells reprogramming towards pluripotency [RNA-seq]

| PRJNA482432 | ENA

Low cytosolic folate cycling is a hallmark of U251 glioblastoma cells reprogramming towards pluripotency

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-07-01 | GSE117544 | GEO

Tumor reliance on cytosolic versus mitochondrial one-carbon flux depends on folate availability

Project description:Tumor reliance on cytosolic versus mitochondrial one-carbon flux depends on folate availability

| PRJNA641374 | ENA

Tumor reliance on cytosolic versus mitochondrial one-carbon flux depends on folate availability

Project description:The goal of this analysis is to detect the differentially expressed genes between cells cultured in high or low folate condition.

2020-06-24 | GSE153023 | GEO

Expression data from U251-shCtrl and U251-shCPVL cells

Project description:we performed microarray expression profiling to analyze the differentially expressed genes between U251-shCtrl and U251-shCPVL cells.

2024-11-01 | GSE188414 | GEO

RNA sequencing facilitates quantitative analysis of U251-NC and U251-COL8A1 transcriptomes

Project description:To investigate the function of COL8A1 in GSCs progression, we established U251-COL8A1 cell lines with COL8A1 overexpressed. Then we performed gene expression profiling analysis using data obtained from RNA-seq of 2 cells (U251NC and U251-COL8A1)

2024-07-01 | GSE246528 | GEO

Expression data from U251-shCtrl and U251-shCPVL cells

Project description:Expression data from U251-shCtrl and U251-shCPVL cells

| PRJNA778755 | ENA