Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ARRB1 Regulates Metabolic Reprogramming to Promote Glycolysis in Stem Cell-Like Bladder Cancer Cells.

ABSTRACT: β-arrestin 1 (ARRB1) is a scaffold protein that regulates signaling downstream of G protein-coupled receptors (GPCRs). In the current work, we investigated the role of ARRB1 in regulating the metabolic preference of cancer stem cell (CSC)-like cells in bladder cancer (BC). We show that ARRB1 is crucial for spheroid formation and tumorigenic potential. Furthermore, we measured mitochondrial respiration, glucose uptake, glycolytic rate, mitochondrial/glycolytic ATP production and fuel oxidation in previously established ARRB1 knock out (KO) cells and corresponding controls. Our results demonstrate that depletion of ARRB1 decreased glycolytic rate and induced metabolic reprogramming towards oxidative phosphorylation. Mechanistically, the depletion of ARRB1 dramatically increased the mitochondrial pyruvate carrier MPC1 protein levels and reduced the glucose transporter GLUT1 protein levels along with glucose uptake. Overexpression of ARRB1 in ARRB1 KO cells reversed the phenotype and resulted in the upregulation of glycolysis. In conclusion, we show that ARRB1 regulates the metabolic preference of BC CSC-like cells and functions as a molecular switch that promotes reprogramming towards glycolysis by negatively regulating MPC1 and positively regulating GLUT1/ glucose uptake. These observations open new therapeutic avenues for targeting the metabolic preferences of cancer stem cell (CSC)-like BC cells.

SUBMITTER: Mamouni K

PROVIDER: S-EPMC8069028 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

YY1 regulates skeletal muscle regeneration through controlling metabolic reprogramming of stem cells

Project description:Skeletal muscle satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute or chronic injuries. The lineage progression of quiescent SC toward activation, proliferation and differentiation during the regeneration is orchestrated by cascades of transcription factors (TFs). Here we elucidate the function of the transcription factor Yin Yang1 (YY1) in muscle regeneration. Muscle-specific deletion of YY1 in embryonic muscle progenitors leads to severe deformity of diaphragm muscle formation thus postnatal death. Inducible deletion of YY1 in SC almost completely blocks the acute damage induced muscle repair and exacerbates the chronic injury induced dystrophic phenotype. Examination of SC revealed that YY1 loss results in cell autonomous defect in activation and proliferation. Mechanistic search revealed that YY1 binds and represses mitochondrial gene expression. Simultaneously, it also stabilizes Hif1α protein and activates Hif1α mediated glycolytic genes to facilitate a metabolic reprogramming toward glycolysis which is needed for SC proliferation. Altogether our findings have identified YY1 as a key regulator of SC metabolic reprogramming through its dual roles in modulating both mitochondrial and glycolytic pathways.

| S-SCDT-EMBOJ-2018-99727 | biostudies-other

AHR Regulates Metabolic Reprogramming to Promote SIRT1-Dependent Keratinocyte Differentiation.

Project description:Activation of the transcription factor, AHR, in normal human epidermal keratinocytes increased AHR binding in the gene regions of the glucose transporter, SLC2A1, and the glycolytic enzyme, ENO1. This increased chromatin binding corresponded with AHR-dependent decreases in levels of SLC2A1 and ENO1 mRNA, protein, and activities. Studies of the ENO1 promoter showed activation of the AHR decreases the transcription of ENO1. Glycolysis was lowered by activation of the AHR as measured by decreases in glucose uptake and the production of pyruvate and lactate. Levels of ATP were also decreased. Downregulation of glucose metabolism, either by activation of the AHR, inhibition of glycolysis, inhibition of glucose transport, or inhibition of enolase, increased SIRT1 protein levels in normal human epidermal keratinocytes and the immortalized keratinocyte cell line, N/TERT-1. This increase in SIRT1 was abrogated by the addition of exogenous pyruvate. Moreover, keratinocyte differentiation in response to downregulation of glycolysis, either by activation of the AHR, inhibition of glucose transport, or inhibition of enolase, was dependent on SIRT1. These results indicate that regulation of glycolysis controls keratinocyte differentiation, and that activation of the AHR, by lowering the expression of SLC2A1 and ENO1, can determine this fate.

| S-EPMC6431567 | biostudies-literature

TNFAIP8 drives metabolic reprogramming to promote prostate cancer cell proliferation.

Project description:Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is a member of TIPE/TNFAIP8 family, has been involved in the development and progression of various human cancers. We hypothesized that TNFAIP8 promotes prostate cancer (PCa) progression via regulation of oxidative phosphorylation (OXPHOS) and glycolysis. Ectopic expression of TNFAIP8 increased PCa cell proliferation/migration/spheroid formation by enhancing cell metabolic activities. Mechanistically, TNFAIP8 activated the PI3K-AKT pathway and up-regulated PCa cell survival. TNFAIP8 was also found to regulate the expression of glucose metabolizing enzymes, enhancing glucose consumption, and endogenous ATP production. Treatment with a glycolysis inhibitor, 2-deoxyglucose (2-DG), reduced TNFAIP8 mediated glucose consumption, ATP production, spheroid formation, and PCa cell migration. By maintaining mitochondrial membrane potential, TNFAIP8 increased OXPHOS and glycolysis. Moreover, TNFAIP8 modulates the production of glycolytic metabolites in PCa cells. Collectively, our data suggest that TNFAIP8 exerts its oncogenic effects by enhancing glucose metabolism and by facilitating metabolic reprogramming in PCa cells. Therefore, TNFAIP8 may be a biomarker associated with prostate cancer and indicate a potential therapeutic target.

| S-EPMC7770075 | biostudies-literature

MiR-106b-5p Regulates the Reprogramming of Spermatogonial Stem Cells into iPSC (Induced Pluripotent Stem Cell)-Like Cells

Project description:BackgroundRecent years have brought notable progress in raising the efficiency of the reprogramming technique so that approaches have evolved from known transgenic factors to only a few miRNAs. Nevertheless, there is a poor understanding of both the key factors and biological networks underlying this reprogramming. The present study aimed to investigate the potential of miR-106b-5p in regulating spermatogonial stem cells (SSCs) to induced pluripotent stem cell (iPSC)-like cells.MethodsWe used SSCs because pluripotency is inducible in SSCs under defined culture conditions, and they have a few issues compared to other adult stem cells. As both signaling and post-transcriptional gene controls are critical for pluripotency regulation, we traced the expression of Oct-4, Sox-2, Klf-4, c-Myc, and Nanog (OSKMN). Besides, we considered miR-106b-5p targets using bioinformatic methods.ResultsOur results showed that transfected SSCs with miR-106b-5p increased the expression of the OSKMN factors, which was significantly more than negative control groups. Moreover, using the functional miRNA enrichment analysis, online tools, and databases, we predicted that miR-106b-5p targeted a signaling pathway gene named MAPK1/ERK2, related to regulating stem cell pluripotency.ConclusionTogether, our data suggest that miR-106b-5p regulates the reprogramming of SSCs into iPSC-like cells. Furthermore, noteworthy progress in the in vitro development of SSCs indicates promise reservoirs and opportunities for future clinical trials.

| S-EPMC9432470 | biostudies-literature

P2RX7 signaling drives the differentiation of Th1 cells through metabolic reprogramming for aerobic glycolysis.

Project description:IntroductionThis study provides evidence of how Th1 cell metabolism is modulated by the purinergic receptor P2X7 (P2RX7), a cation cannel activated by high extracellular concentrations of adenosine triphosphate (ATP).MethodsIn vivo analysis was performed in the Plasmodium chabaudi model of malaria in view of the great relevance of this infectious disease for human health, as well as the availability of data concerning Th1/Tfh differentiation.ResultsWe show that P2RX7 induces T-bet expression and aerobic glycolysis in splenic CD4+ T cells that respond to malaria, at a time prior to Th1/Tfh polarization. Cell-intrinsic P2RX7 signaling sustains the glycolytic pathway and causes bioenergetic mitochondrial stress in activated CD4+ T cells. We also show in vitro the phenotypic similarities of Th1-conditioned CD4+ T cells that do not express P2RX7 and those in which the glycolytic pathway is pharmacologically inhibited. In addition, in vitro ATP synthase blockade and the consequent inhibition of oxidative phosphorylation, which drives cellular metabolism for aerobic glycolysis, is sufficient to promote rapid CD4+ T cell proliferation and polarization to the Th1 profile in the absence of P2RX7.ConclusionThese data demonstrate that P2RX7-mediated metabolic reprograming for aerobic glycolysis is a key event for Th1 differentiation and suggest that ATP synthase inhibition is a downstream effect of P2RX7 signaling that potentiates the Th1 response.

| S-EPMC10040773 | biostudies-literature

Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation.

Project description:Histone acetylation plays important roles in gene regulation, DNA replication, and the response to DNA damage, and it is frequently deregulated in tumors. We postulated that tumor cell histone acetylation levels are determined in part by changes in acetyl coenzyme A (acetyl-CoA) availability mediated by oncogenic metabolic reprogramming. Here, we demonstrate that acetyl-CoA is dynamically regulated by glucose availability in cancer cells and that the ratio of acetyl-CoA:coenzyme A within the nucleus modulates global histone acetylation levels. In vivo, expression of oncogenic Kras or Akt stimulates histone acetylation changes that precede tumor development. Furthermore, we show that Akt's effects on histone acetylation are mediated through the metabolic enzyme ATP-citrate lyase and that pAkt(Ser473) levels correlate significantly with histone acetylation marks in human gliomas and prostate tumors. The data implicate acetyl-CoA metabolism as a key determinant of histone acetylation levels in cancer cells.

| S-EPMC4151270 | biostudies-literature

Multiomic Profiling of Tyrosine Kinase Inhibitor-Resistant K562 Cells Suggests Metabolic Reprogramming To Promote Cell Survival.

Project description:Resistance to chemotherapy can occur through a wide variety of mechanisms. Resistance to tyrosine kinase inhibitors (TKIs) often arises from kinase mutations-however, "off-target" resistance occurs but is poorly understood. Previously, we established cell line resistance models for three TKIs used in chronic myeloid leukemia treatment, and found that resistance was not attributed entirely to failure of kinase inhibition. Here, we performed global, integrated proteomic and transcriptomic profiling of these cell lines to describe mechanisms of resistance at the protein and gene expression level. We used whole transcriptome sequencing and SWATH-based data-independent acquisition mass spectrometry (DIA-MS), which does not require isotopic labels and provides quantitative measurements of proteins in a comprehensive, unbiased fashion. The proteomic and transcriptional data were correlated to generate an integrated understanding of the gene expression and protein alterations associated with TKI resistance. We defined mechanisms of resistance and two novel markers, CA1 and alpha-synuclein, that were common to all TKIs tested. Resistance to all of the TKIs was associated with oxidative stress responses, hypoxia signatures, and apparent metabolic reprogramming of the cells. Metabolite profiling and glucose-dependence experiments showed that resistant cells had routed their metabolism through glycolysis (particularly through the pentose phosphate pathway) and exhibited disruptions in mitochondrial metabolism. These experiments are the first to report a global, integrated proteomic, transcriptomic, and metabolic analysis of TKI resistance. These data suggest that although the mechanisms are complex, targeting metabolic pathways along with TKI treatment may overcome pan-TKI resistance.

| S-EPMC7250065 | biostudies-literature

Bladder Cancer-Derived Small Extracellular Vesicles Promote Tumor Angiogenesis by Inducing HBP-Related Metabolic Reprogramming and SerRS O-GlcNAcylation in Endothelial Cells.

Project description:A malformed tumour vascular network provokes the nutrient-deprived tumour microenvironment (TME), which conversely activates endothelial cell (EC) functions and stimulates neovascularization. Emerging evidence suggests that the flexible metabolic adaptability of tumour cells helps to establish a metabolic symbiosis among various cell subpopulations in the fluctuating TME. In this study, the authors propose a novel metabolic link between bladder cancer (BCa) cells and ECs in the nutrient-scarce TME, in which BCa-secreted glutamine-fructose-6-phosphate aminotransferase 1 (GFAT1) via small extracellular vesicles (sEVs) reprograms glucose metabolism by increasing hexosamine biosynthesis pathway flux in ECs and thus enhances O-GlcNAcylation. Moreover, seryl-tRNA synthetase (SerRS) O-GlcNAcylation at serine 101 in ECs promotes its degradation by ubiquitination and impeded importin α5-mediated nuclear translocation. Intranuclear SerRS attenuates vascular endothelial growth factor transcription by competitively binding to the GC-rich region of the proximal promotor. Additionally, GFAT1 knockout in tumour cells blocks SerRS O-GlcNAcylation in ECs and attenuates angiogenesis both in vitro and in vivo. However, administration of GFAT1-overexpressing BCa cells-derived sEVs increase the angiogenetic activity in the ECs of GFAT1-knockout mice. In summary, this study suggests that inhibiting sEV-mediated GFAT1 secretion from BCa cells and targeting SerRS O-GlcNAcylation in ECs may serve as novel strategies for BCa antiangiogenetic therapy.

| S-EPMC9596856 | biostudies-literature

ATF4 Regulates CD4+ T Cell Immune Responses through Metabolic Reprogramming.

Project description:T cells are strongly regulated by oxidizing environments and amino acid restriction. How T cells reprogram metabolism to adapt to these extracellular stress situations is not well understood. Here, we show that oxidizing environments and amino acid starvation induce ATF4 in CD4+ T cells. We also demonstrate that Atf4-deficient CD4+ T cells have defects in redox homeostasis, proliferation, differentiation, and cytokine production. We further reveal that ATF4 regulates a coordinated gene network that drives amino acid intake, mTORC1 activation, protein translation, and an anabolic program for de novo synthesis of amino acids and glutathione. ATF4 also promotes catabolic glycolysis and glutaminolysis and oxidative phosphorylation and thereby provides precursors and energy for anabolic pathways. ATF4-deficient mice mount reduced Th1 but elevated Th17 immune responses and develop more severe experimental allergic encephalomyelitis (EAE). Our study demonstrates that ATF4 is critical for CD4+ T cell-mediated immune responses through driving metabolic adaptation.

| S-EPMC6051420 | biostudies-literature

miR-142 controls metabolic reprogramming that regulates dendritic cell activation.

Project description:DCs undergo metabolic reprogramming from a predominantly oxidative phosphorylation (OXPHOS) to glycolysis to mount an immunogenic response. The mechanism underpinning the metabolic reprogramming remains elusive. We demonstrate that miRNA-142 (miR-142) is pivotal for this shift in metabolism, which regulates the tolerogenic and immunogenic responses of DCs. In the absence of miR-142, DCs fail to switch from OXPHOS and show reduced production of proinflammatory cytokines and the ability to activate T cells in vitro and in in vivo models of sepsis and alloimmunity. Mechanistic studies demonstrate that miR-142 regulates fatty acid (FA) oxidation, which causes the failure to switch to glycolysis. Loss- and gain-of-function experiments identified carnitine palmitoyltransferase -1a (CPT1a), a key regulator of the FA pathway, as a direct target of miR-142 that is pivotal for the metabolic switch. Thus, our findings show that miR-142 is central to the metabolic reprogramming that specifically favors glycolysis and immunogenic response by DCs.

| S-EPMC6486330 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data