2025
Senescence Cell Induction Methods Display Diverse Metabolic Reprogramming and Reveal an Underpinning Serine/Taurine Reductive Metabolic Phenotype
Berardi D, Farrell G, AlSultan A, McCulloch A, Hall N, Sousa R, Jimenez M, Selman C, Bellantuono I, Johnson C, Rattray Z, Rattray N. Senescence Cell Induction Methods Display Diverse Metabolic Reprogramming and Reveal an Underpinning Serine/Taurine Reductive Metabolic Phenotype. Aging Cell 2025, e70127. PMID: 40530891, DOI: 10.1111/acel.70127.Peer-Reviewed Original ResearchSenescence inductionLabel-free proteomicsDNA damage markersRedox circuitsCell inductionImpaired proteostasisP21 levelsTherapeutic strategiesCellular phenotypesMetabolic phenotypeMetabolic reprogrammingProteomic heterogeneityMetabolic shiftSenescence markersProteomic profilingMetabolic processesSenescence biomarkersDamage markersProtein levelsSenescenceSubphenotypesSenescence modelInfluence cellsPhenotypeInductionIndole-3-lactic acid suppresses colorectal cancer via metabolic reprogramming
Zhou S, Wang K, Huang J, Xu Z, Yuan Q, Liu L, Wang Z, Miao J, Wang H, Wang T, Guan W, Ding C. Indole-3-lactic acid suppresses colorectal cancer via metabolic reprogramming. Gut Microbes 2025, 17: 2508949. PMID: 40409349, PMCID: PMC12118437, DOI: 10.1080/19490976.2025.2508949.Peer-Reviewed Original ResearchConceptsIndole-3-lactic acidColorectal cancer patientsColorectal cancerAryl hydrocarbon receptorDownregulated glucose metabolismPotential clinical therapeutic targetsAnti-apoptotic capabilityInfluence tumor progressionGut microbiota metabolismTumor cell proliferationMetagenomic sequencingPhosphorylation sitesXenograft mouse modelGut microbiotaClinical therapeutic targetMetabolic reprogrammingMicrobiota metabolismP-STAT3Tumor progressionTumor malignancyMouse modelTryptophan metabolismCancer cellsIn vitro experimentsCRC developmentAdding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury
Baker M, Cantley L. Adding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury. Journal Of Clinical Investigation 2025, 135: e188358. PMID: 40091836, PMCID: PMC11910233, DOI: 10.1172/jci188358.Peer-Reviewed Original ResearchConceptsAcute kidney injuryTubular epithelial cellsKidney injuryTubular cellsCases of acute kidney injuryImmune-mediated processPersistence of inflammationBiphasic immune responseChronic kidney diseaseCell deathTubular cell injuryLymphocyte subsetsTubular repairCell cycle arrestOutflow obstructionTEC differentiationPreclinical findingsLymphocytic infiltrationProinflammatory macrophagesKidney diseaseModulate inflammationImmune responseActivated macrophagesMetabolic reprogrammingTubular caststRNA m1A modification regulates cholesterol biosynthesis to promote antitumor immunity of CD8+ T cells
Miao S, Li H, Song X, Liu Y, Wang G, Kan C, Ye Y, Liu R, Li H. tRNA m1A modification regulates cholesterol biosynthesis to promote antitumor immunity of CD8+ T cells. Journal Of Experimental Medicine 2025, 222: e20240559. PMID: 39873720, PMCID: PMC11774205, DOI: 10.1084/jem.20240559.Peer-Reviewed Original ResearchConceptsCD8+ T cellsT cellsTumor-killing functionTransfer RNARegulating cholesterol biosynthesisAntitumor immunityCapacity of CD8+ T cellsActivation of CD8+ T cellsCholesterol biosynthesisM1A modificationTumor-killing capacityAntitumor responseATP citrate lyaseCancer immunotherapyCD8Effector functionsMetabolic reprogrammingProtein translationBiosynthetic demandsCitrate lyaseIn vitro assaysIn vivoPosttranscriptional mechanismsRegulatory checkpointsBiosynthesis
2024
Bacterial reprogramming of tick metabolism impacts vector fitness and susceptibility to infection
Samaddar S, Rolandelli A, O’Neal A, Laukaitis-Yousey H, Marnin L, Singh N, Wang X, Butler L, Rangghran P, Kitsou C, Cabrera Paz F, Valencia L, R. Ferraz C, Munderloh U, Khoo B, Cull B, Rosche K, Shaw D, Oliver J, Narasimhan S, Fikrig E, Pal U, Fiskum G, Polster B, Pedra J. Bacterial reprogramming of tick metabolism impacts vector fitness and susceptibility to infection. Nature Microbiology 2024, 9: 2278-2291. PMID: 38997520, PMCID: PMC11926704, DOI: 10.1038/s41564-024-01756-0.Peer-Reviewed Original ResearchMetabolic reprogrammingInfection of tick cellsInvestigate metabolic reprogrammingTick cellsLyme disease spirochete Borrelia burgdorferiSusceptibility to infectionArthropod-borne pathogensMetabolomics approachRickettsia buchneriHuman pathogensMetabolite allocationDiminished survivalBacterium Anaplasma phagocytophilumSpirochete Borrelia burgdorferiAcid metabolismA. phagocytophilum infectionInterspecies relationshipsElevated levelsInfectionFeeding impairmentHuman granulocytic anaplasmosisMetabolic responseArthropod vectorsI. scapularisPathogensGrowth characteristics of HCT116 xenografts lacking asparagine synthetase vary according to sex
Aladelokun O, Lu L, Zheng J, Yan H, Jain A, Gibson J, Khan S, Johnson C. Growth characteristics of HCT116 xenografts lacking asparagine synthetase vary according to sex. Human Genomics 2024, 18: 67. PMID: 38886847, PMCID: PMC11184737, DOI: 10.1186/s40246-024-00635-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAspartate-Ammonia LigaseCarbon-Nitrogen Ligases with Glutamine as Amide-N-DonorCell ProliferationColorectal NeoplasmsFemaleGene Expression Regulation, NeoplasticHCT116 CellsHeterograftsHumansMaleMiceReceptors, EstrogenReceptors, G-Protein-CoupledSex FactorsXenograft Model Antitumor AssaysConceptsFemale tumor-bearing miceFemale CRC patientsTumor-bearing miceCRC patientsTumor growthInferior survivalAssociated with inferior survivalMetabolic reprogrammingG protein-coupled estrogen receptorTriggering metabolic reprogrammingSustained tumor growthSuppressed tumor growthExpression of asparagine synthetaseCancer cell linesBackgroundSex-related differencesSurvival improvementImpact of sexFemale miceEstrogen receptorCancer growthTranslational relevanceRewiring of metabolic pathwaysCancer burdenMetabolic pathwaysAsparagine synthetaseTransmembrane pH gradient imaging in rodent glioma models
Mishra S, Santana J, Mihailovic J, Hyder F, Coman D. Transmembrane pH gradient imaging in rodent glioma models. NMR In Biomedicine 2024, 37: e5102. PMID: 38263680, PMCID: PMC10987279, DOI: 10.1002/nbm.5102.Peer-Reviewed Original ResearchNormal tissuesRodent glioma modelsGL261 gliomasU87 gliomasTumor microenvironmentPotential therapeutic targetGlioma modelTumor survivalExtracellular acidosisTumorMetabolic reprogrammingRegulate drug deliveryIntracellular pHRat brainExtracellular pHTherapeutic targetGliomaMouse brainDrug deliveryIntracellular milieuTransmembrane pH gradientBrainSubmillimeter resolutionTissueCells
2023
Molecular Mechanism of Fasting-Mimicking Diet in Inhibiting Colorectal Cancer Progression: Implications for Immune Therapy and Metabolic Regulation.
Bush C, Perry R. Molecular Mechanism of Fasting-Mimicking Diet in Inhibiting Colorectal Cancer Progression: Implications for Immune Therapy and Metabolic Regulation. Cancer Research 2023, 83: 3493-3494. PMID: 37908187, DOI: 10.1158/0008-5472.can-23-2257.Commentaries, Editorials and LettersConceptsFasting-mimicking dietColorectal cancer progressionIgA class switchingColorectal cancerCancer progressionB cellsClass switchingFatty acid oxidationAnticancer immunityAntitumor immunityImmune therapyMolecular mechanismsTumor regressionMouse modelCaloric restrictionAnticancer effectsMetabolic reprogrammingProgressionDietCancerAcid oxidationCancer researchImmunityMetabolic regulationCellsTargeted Proteomic Quantitation of NRF2 Signaling and Predictive Biomarkers in HNSCC
Wamsley N, Wilkerson E, Guan L, LaPak K, Schrank T, Holmes B, Sprung R, Gilmore P, Gerndt S, Jackson R, Paniello R, Pipkorn P, Puram S, Rich J, Townsend R, Zevallos J, Zolkind P, Le Q, Goldfarb D, Major M. Targeted Proteomic Quantitation of NRF2 Signaling and Predictive Biomarkers in HNSCC. Molecular & Cellular Proteomics 2023, 22: 100647. PMID: 37716475, PMCID: PMC10587640, DOI: 10.1016/j.mcpro.2023.100647.Peer-Reviewed Original ResearchConceptsHead and neck squamous cell carcinomaHuman papilloma virus infection statusNeck squamous cell carcinomaProtein expressionT cell infiltrationSquamous cell carcinomaGene expression programsCancer cell modelsSOX2 protein expressionPromote cancer progressionTranscription factorsResponse proteinsPathway componentsMetabolic reprogrammingVirus infection statusCell carcinomaPredictive biomarkersChemoradiation resistanceExpression programsProteomic assaysE7 proteinProtein biomarker assaysImmune evasionPatient stratificationClinical significanceMetabolic reprogramming by immune-responsive gene 1 up-regulation improves donor heart preservation and function
Lei I, Huang W, Noly P, Naik S, Ghali M, Liu L, Pagani F, Abou El Ela A, Pober J, Pitt B, Platt J, Cascalho M, Wang Z, Chen Y, Mortensen R, Tang P. Metabolic reprogramming by immune-responsive gene 1 up-regulation improves donor heart preservation and function. Science Translational Medicine 2023, 15: eade3782. PMID: 36753565, PMCID: PMC10068866, DOI: 10.1126/scitranslmed.ade3782.Peer-Reviewed Original ResearchConceptsImmune response gene 1Primary graft dysfunctionDonor heart preservationValproic acidDonor heartsVPA treatmentHeart preservationHeart functionImmune-responsive gene 1Donor heart functionHistone deacetylase inhibitor valproic acidImproved heart functionAntioxidant protein expressionMetabolic reprogrammingDonor-recipient matchingPromising therapeutic strategyHuman donor heartsInhibitor valproic acidGene 1Graft dysfunctionCardioprotective effectsKetoglutarate solutionTherapeutic strategiesResponse gene-1Nuclear factorSodium perturbs mitochondrial respiration and induces dysfunctional Tregs
Côrte-Real B, Hamad I, Arroyo Hornero R, Geisberger S, Roels J, Van Zeebroeck L, Dyczko A, van Gisbergen M, Kurniawan H, Wagner A, Yosef N, Weiss S, Schmetterer K, Schröder A, Krampert L, Haase S, Bartolomaeus H, Hellings N, Saeys Y, Dubois L, Brenner D, Kempa S, Hafler D, Stegbauer J, Linker R, Jantsch J, Müller D, Kleinewietfeld M. Sodium perturbs mitochondrial respiration and induces dysfunctional Tregs. Cell Metabolism 2023, 35: 299-315.e8. PMID: 36754020, DOI: 10.1016/j.cmet.2023.01.009.Peer-Reviewed Original ResearchConceptsHuman TregsPro-inflammatory featuresLong-term dysfunctionPro-inflammatory signatureMetabolic reprogrammingLong-term functionDysfunctional TregsFoxp3 downregulationPeripheral toleranceMitochondrial respirationMetabolic disturbancesTregsImmune functionAutoimmunityMetabolic fitnessIntracellular NaMitochondrial NaHigh saltMitochondrial metabolismElectron transport chainTranscriptional changesFoxp3DysfunctionBlockadeGOT1 regulates CD8+ effector and memory T cell generation
Xu W, Patel C, Zhao L, Sun I, Oh M, Sun I, Helms R, Wen J, Powell J. GOT1 regulates CD8+ effector and memory T cell generation. Cell Reports 2023, 42: 111987. PMID: 36640309, PMCID: PMC9943022, DOI: 10.1016/j.celrep.2022.111987.Peer-Reviewed Original ResearchConceptsIntracellular redox balancePosttranslational regulationHIF proteinsMetabolic reprogrammingRedox balanceΑ-ketoglutarateGOT1T cell activationCell generationGenetic deletionEffector differentiationCritical roleCell activationDifferentiationRegulationProliferationReprogrammingBiosynthesisEffectorsProteinDeletionMechanisticallyCytotoxic functionFunctionPurine
2022
Acetyl-Coenzyme A Synthetase 2 Potentiates Macropinocytosis and Muscle Wasting Through Metabolic Reprogramming in Pancreatic Cancer
Zhou Z, Ren Y, Yang J, Liu M, Shi X, Luo W, Fung K, Xu C, Bronze M, Zhang Y, Houchen C, Li M. Acetyl-Coenzyme A Synthetase 2 Potentiates Macropinocytosis and Muscle Wasting Through Metabolic Reprogramming in Pancreatic Cancer. Gastroenterology 2022, 163: 1281-1293.e1. PMID: 35777482, PMCID: PMC9613512, DOI: 10.1053/j.gastro.2022.06.058.Peer-Reviewed Original ResearchConceptsMetabolic reprogrammingDynamin 2Transcriptional activationShort palindromic repeat-associated protein 9 (CRISPR/Cas9) systemSingle-cell RNA sequencing dataRNA sequencing dataProtein 9 (Cas9) systemGlycogen synthase kinasePancreatic cancerEpigenetic reprogrammingFamily member 2Chromatin immunoprecipitationMuscle wastingDownstream targetsSequencing dataSyndecan-1ReprogrammingSynthase kinaseWorse prognosisMacropinocytosisZIP4ACSS2Mouse modelProtein 4Uptake assaysComprehensive Analysis of Metabolic Isozyme Targets in Cancer
Marczyk M, Gunasekharan V, Casadevall D, Qing T, Foldi J, Sehgal R, Shan NL, Blenman KRM, O'Meara TA, Umlauf S, Surovtseva YV, Muthusamy V, Rinehart J, Perry RJ, Kibbey R, Hatzis C, Pusztai L. Comprehensive Analysis of Metabolic Isozyme Targets in Cancer. Cancer Research 2022, 82: 1698-1711. PMID: 35247885, PMCID: PMC10883296, DOI: 10.1158/0008-5472.can-21-3983.Peer-Reviewed Original ResearchConceptsPotential therapeutic targetAcetyl-CoA carboxylase 1Therapeutic targetCancer typesCell linesBreast cancer viabilityPatient-derived xenograftsNovel metabolic targetsCorresponding cell linesExpression patternsDrug treatmentMatching normal tissuesRelated commentaryTumor growthMalignant transformationSmall molecule inhibitionCancer viabilityCancer Cell Line EncyclopediaNormal tissuesMetabolic vulnerabilitiesCarboxylase 1Anticancer therapyCellular changesCell proliferationMetabolic reprogrammingSOX2 mediates metabolic reprogramming of prostate cancer cells
de Wet L, Williams A, Gillard M, Kregel S, Lamperis S, Gutgesell L, Vellky J, Brown R, Conger K, Paner G, Wang H, Platz E, De Marzo A, Mu P, Coloff J, Szmulewitz R, Vander Griend D. SOX2 mediates metabolic reprogramming of prostate cancer cells. Oncogene 2022, 41: 1190-1202. PMID: 35067686, PMCID: PMC8858874, DOI: 10.1038/s41388-021-02157-x.Peer-Reviewed Original ResearchConceptsProstate cancer cellsSOX2 expressionCancer cellsTherapy resistanceMetastatic progressionMetabolic reprogrammingAssociated with multiple oncogenic pathwaysAndrogen-sensitive prostate cancer cellsGene targetingCastration-resistant prostate cancer cellsIncreased spare respiratory capacityChIP-seq analysisRNA-seq datasetsStem cell transcription factor Sox2Prostate cancer cell linesAnnotated tumor specimensSOX2 binding sitesPentose phosphate pathwayCRISPR-mediated deletionDecreased patient survivalSpare respiratory capacityQuantity of mitochondriaDeletion of Sox2Case-control cohortGene expression analysisMagnesium sensing via LFA-1 regulates CD8+ T cell effector function
Lötscher J, Martí I Líndez AA, Kirchhammer N, Cribioli E, Giordano Attianese G, Trefny MP, Lenz M, Rothschild SI, Strati P, Künzli M, Lotter C, Schenk SH, Dehio P, Löliger J, Litzler L, Schreiner D, Koch V, Page N, Lee D, Grählert J, Kuzmin D, Burgener AV, Merkler D, Pless M, Balmer ML, Reith W, Huwyler J, Irving M, King CG, Zippelius A, Hess C. Magnesium sensing via LFA-1 regulates CD8+ T cell effector function. Cell 2022, 185: 585-602.e29. PMID: 35051368, DOI: 10.1016/j.cell.2021.12.039.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial InfectionsCaloric RestrictionCD8-Positive T-LymphocytesCell Line, TumorCytotoxicity, ImmunologicHEK293 CellsHumansImmunologic MemoryImmunological SynapsesImmunotherapyLymphocyte ActivationLymphocyte Function-Associated Antigen-1MagnesiumMaleMAP Kinase Signaling SystemMice, Inbred C57BLNeoplasmsPhenotypePhosphorylationProto-Oncogene Proteins c-junConceptsLFA-1CAR TLow serum magnesium levelsMore rapid disease progressionAntibody-treated patientsRapid disease progressionShorter overall survivalSerum magnesium levelsCell effector functionsOverall survivalCellular immunityImmune synapse formationDisease progressionEffector functionsExtracellular magnesiumSpecific cytotoxicityMagnesium levelsSynapse formationCalcium fluxCell functionMetabolic reprogrammingCD8CellsNutrient sensingPatients
2021
m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity
Qin Y, Li B, Arumugam S, Lu Q, Mankash SM, Li J, Sun B, Li J, Flavell RA, Li HB, Ouyang X. m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity. Cell Reports 2021, 37: 109968. PMID: 34758326, PMCID: PMC8667589, DOI: 10.1016/j.celrep.2021.109968.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseProgression of NAFLDLineage-restricted deletionFatty liver diseaseMultiple mRNA transcriptsMyeloid cell activationDiet-induced developmentMethyladenosine (m<sup>6</sup>A) RNA modificationMRNA metabolismProtein methyltransferaseLiver diseaseRNA modificationsCellular stressMetabolic reprogrammingDDIT4 mRNACell activationObesityDifferential expressionMammalian targetMRNA transcriptsSignificant downregulationCytokine stimulationPathway activityMetabolic phenotypeMRNA levelsEndothelial SIRT3 regulates myofibroblast metabolic shifts in diabetic kidneys
Srivastava SP, Li J, Takagaki Y, Kitada M, Goodwin JE, Kanasaki K, Koya D. Endothelial SIRT3 regulates myofibroblast metabolic shifts in diabetic kidneys. IScience 2021, 24: 102390. PMID: 33981977, PMCID: PMC8086030, DOI: 10.1016/j.isci.2021.102390.Peer-Reviewed Original ResearchDiabetic kidney fibrosisDiabetic kidneyEndothelial cellsKidney fibrosisDefective metabolismRenal tubular epithelial cellsTubular epithelial cellsKidney functionDiabetic miceFibrogenic pathwaysFibrogenic processDisease processLoss of functionMesenchymal transitionKidneyMouse strainsEpithelial cellsGain of functionSIRT3Metabolic reprogrammingMesenchymal transformationFibrosisSIRT3 geneMetabolismCellsThe Complex Integration of T-cell Metabolism and Immunotherapy
Madden M, Rathmell J. The Complex Integration of T-cell Metabolism and Immunotherapy. Cancer Discovery 2021, 11: 1636-1643. PMID: 33795235, PMCID: PMC8295173, DOI: 10.1158/2159-8290.cd-20-0569.Peer-Reviewed Original ResearchConceptsT cell metabolismT cell functionT cellsImmune-oncology approachesEffector T cellsOxidative metabolismAdoptive cell therapyT cell interactionsT cell fateAntitumor immunityCancer immunotherapyImmune oncologyTumor microenvironmentNormal stimulationCell therapyTumorsAerobic glycolysisMetabolic reprogrammingMetabolic reprogramming eventsImmunotherapyMetabolismCellsTherapyCancerCentral roleImaging extracellular acidification and immune activation in cancer
Hyder F, Coman D. Imaging extracellular acidification and immune activation in cancer. Current Opinion In Biomedical Engineering 2021, 18: 100278. PMID: 33997581, PMCID: PMC8115219, DOI: 10.1016/j.cobme.2021.100278.Peer-Reviewed Original ResearchGene-centric viewMetabolic reprogrammingHostile ecosystemCancer hallmarksHabitat acidificationHost cellsFuture cancer therapyAerobic glycolysisDiverse mechanismsMetabolic interactionsExtracellular acidificationDifferent nutrientsCancer cellsImmune cellsDisease tissuesCellsTumor milieuNutrientsCancer therapyMetabolismRecent evidenceIncidental phenomenonAcidificationReprogrammingOncogene
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