2025
Lipogenic enzyme FASN promotes mutant p53 accumulation and gain-of-function through palmitoylation
Liu J, Shen Y, Liu J, Xu D, Chang C, Wang J, Zhou J, Haffty B, Zhang L, Bargonetti J, De S, Hu W, Feng Z. Lipogenic enzyme FASN promotes mutant p53 accumulation and gain-of-function through palmitoylation. Nature Communications 2025, 16: 1762. PMID: 39971971, PMCID: PMC11839913, DOI: 10.1038/s41467-025-57099-9.Peer-Reviewed Original ResearchConceptsGain-of-functionTumor suppressive function of p53Mutp53 accumulationAccumulate to high levelsFunction of p53Mutant p53 accumulationTumor suppressive functionMutant p53Subcutaneous xenograft tumor modelMutp53Promote tumorigenesisP53 accumulationPalmitoylationPotential therapeutic strategyXenograft tumor modelFASNTumor modelTumor organoidsTransgenic miceTherapeutic strategiesP53Sorafenib Alters Interstitial Proton and Sodium Levels in the Tumor Microenvironment: A 1H/23Na Spectroscopic Imaging Study
Khan M, Walsh J, Kurdi S, Mishra S, Mihailović J, Coman D, Hyder F. Sorafenib Alters Interstitial Proton and Sodium Levels in the Tumor Microenvironment: A 1H/23Na Spectroscopic Imaging Study. NMR In Biomedicine 2025, 38: e5319. PMID: 39764672, DOI: 10.1002/nbm.5319.Peer-Reviewed Original ResearchConceptsU87 tumorsSorafenib-treated tumorsUpregulated aerobic glycolysisSodium-potassium pumpInterstitial spaceTumor microenvironmentIntracellular NaTumor growthSpectroscopic imaging studiesTumor invasionGlioblastoma modelSodium levelsTumorGlioblastoma therapyImaging studiesPlaceboSorafenibMetabolic changesImmune functionCancer hallmarksAerobic glycolysisProliferative stateMeasure treatment effectsIonic changesProliferation rate
2024
Tertiary amine modification enables triterpene nanoparticles to target the mitochondria and treat glioblastoma via pyroptosis induction
Gao X, Tang X, Tu Z, Yu J, Bao Y, Long G, Sheu W, Wu H, Liu J, Zhou J. Tertiary amine modification enables triterpene nanoparticles to target the mitochondria and treat glioblastoma via pyroptosis induction. Biomaterials 2024, 317: 123035. PMID: 39731842, PMCID: PMC11827167, DOI: 10.1016/j.biomaterials.2024.123035.Peer-Reviewed Original ResearchConceptsSurvival of tumor-bearing miceBrain tumorsEffective treatmentPenetrate brain tumorsEffective treatment of glioblastomaTumor-bearing micePrimary brain tumorTreatment of glioblastomaMitochondria-targeted effectsTreating glioblastomaCancer treatmentGlioblastomaEffective killingTherapeutic targetHexokinase inhibitorGBM cellsPyroptosis inductionMitochondriaTumorGlycyrrhetinic acidTargeting effectTreatmentComparative Kidney Uptake of Nanobody-Based PET Tracers Labeled with Various Fluorine-18-Labeled Prosthetic Groups
Olkowski C, Basuli F, Fernandes B, Ghaemi B, Shi J, Zhang H, Farber J, Escorcia F, Choyke P, Jacobson O. Comparative Kidney Uptake of Nanobody-Based PET Tracers Labeled with Various Fluorine-18-Labeled Prosthetic Groups. Molecular Pharmaceutics 2024, 22: 533-543. PMID: 39680709, DOI: 10.1021/acs.molpharmaceut.4c01101.Peer-Reviewed Original ResearchAcyl-CoA Synthetase Medium-Chain Family Member 5–Mediated Fatty Acid Metabolism Dysregulation Promotes the Progression of Hepatocellular Carcinoma
Yang L, Pham K, Xi Y, Jiang S, Robertson K, Liu C. Acyl-CoA Synthetase Medium-Chain Family Member 5–Mediated Fatty Acid Metabolism Dysregulation Promotes the Progression of Hepatocellular Carcinoma. American Journal Of Pathology 2024, 194: 1951-1966. PMID: 39069168, PMCID: PMC11423759, DOI: 10.1016/j.ajpath.2024.07.002.Peer-Reviewed Original ResearchConceptsDNA methyltransferase 1Fatty acid metabolismAcyl-CoADown-regulationAcid metabolismDecreased STAT3 phosphorylationCell linesPromoter region methylationHepatocellular carcinoma cell lineHepatocellular carcinoma patient samplesDNA methylationFatty acid accumulationDysregulated fatty acid metabolismSTAT3 phosphorylationDecreased cell proliferationHepatocellular carcinomaHepatocellular carcinoma tumor tissuesMethyltransferase 1Region methylationRegulatory mechanismsACSM5Molecular mechanismsMetabolic dysregulationProgression of hepatocellular carcinomaAcid accumulationPRMT6 facilitates EZH2 protein stability by inhibiting TRAF6-mediated ubiquitination degradation to promote glioblastoma cell invasion and migration
Wang J, Shen S, You J, Wang Z, Li Y, Chen Y, Tuo Y, Chen D, Yu H, Zhang J, Wang F, Pang X, Xiao Z, Lan Q, Wang Y. PRMT6 facilitates EZH2 protein stability by inhibiting TRAF6-mediated ubiquitination degradation to promote glioblastoma cell invasion and migration. Cell Death & Disease 2024, 15: 524. PMID: 39043634, PMCID: PMC11266590, DOI: 10.1038/s41419-024-06920-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsCell Line, TumorCell MovementEnhancer of Zeste Homolog 2 ProteinFemaleGene Expression Regulation, NeoplasticGlioblastomaHumansMaleMiceMice, Inbred BALB CMice, NudeNeoplasm InvasivenessNuclear ProteinsProtein StabilityProtein-Arginine N-MethyltransferasesProteolysisTNF Receptor-Associated Factor 6UbiquitinationConceptsProtein arginine methyltransferase 6Glioblastoma cell invasionStability of EZH2Protein stabilityCell invasionOverexpression of PRMT6Inhibited glioblastoma cell invasionGlioblastoma cellsEZH2 protein stabilityHistone methylation marksMigration of glioblastoma cellsHallmarks of cancerProliferation of glioblastoma cellsMethylation marksTumor cell invasionEpigenetic regulationGlioblastoma cells in vivoBioinformatics analysisMigration in vitroRegulatory relationshipsEZH2 proteinUbiquitination degradationProteinCells in vivoTRAF6PROTAC EZH2 degrader-1 overcomes the resistance of podophyllotoxin derivatives in refractory small cell lung cancer with leptomeningeal metastasis
Shi M, Ding X, Tang L, Cao W, Su B, Zhang J. PROTAC EZH2 degrader-1 overcomes the resistance of podophyllotoxin derivatives in refractory small cell lung cancer with leptomeningeal metastasis. BMC Cancer 2024, 24: 504. PMID: 38644473, PMCID: PMC11034131, DOI: 10.1186/s12885-024-12244-3.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerCell lung cancerMouse modelLung cancerRefractory small cell lung cancerNude miceIn vivo drug testingCell linesDrug testingLM cellsSensitivity of cisplatinIn vitro drug testingIncreased in vitroBackgroundLeptomeningeal metastasisLeptomeningeal metastasesSevere neurological disordersAssociated with several neurological disordersDrug sensitivityIn vivo live imagingHistological examinationCarotid arteryEffective treatmentMetastasisDrug trialsExpressing luciferase
2022
Subcellular progression of mesenchymal transition identified by two discrete synchronous cell lines derived from the same glioblastoma
Kim S, Park S, Chowdhury T, Hong J, Ahn J, Jeong T, Yu H, Shin Y, Ku J, Park J, Hur J, Lee H, Kim K, Park C. Subcellular progression of mesenchymal transition identified by two discrete synchronous cell lines derived from the same glioblastoma. Cellular And Molecular Life Sciences 2022, 79: 181. PMID: 35278143, PMCID: PMC8918182, DOI: 10.1007/s00018-022-04188-3.Peer-Reviewed Original ResearchConceptsMesenchymal transitionCell linesAvailable single-cell RNA-seq dataMesenchymal transition (EMT) processCancer cell linesSame tissue samplesTherapeutic implicationsTumor samplesRecurrent samplesDriver mutationsGlioblastomaTissue samplesDistinct cancer cell linesGBM samplesIntratumoral heterogeneityTranscriptomic characteristics
2021
Vulnerability of IDH1-Mutant Cancers to Histone Deacetylase Inhibition via Orthogonal Suppression of DNA Repair
Dow J, Krysztofiak A, Liu Y, Colon-Rios DA, Rogers FA, Glazer PM. Vulnerability of IDH1-Mutant Cancers to Histone Deacetylase Inhibition via Orthogonal Suppression of DNA Repair. Molecular Cancer Research 2021, 19: 2057-2067. PMID: 34535560, PMCID: PMC8642278, DOI: 10.1158/1541-7786.mcr-21-0456.Peer-Reviewed Original ResearchConceptsHistone deacetylase inhibitor vorinostatPatient-derived tumor xenograftsHomology-directed repairIsocitrate dehydrogenase 1/2 mutationsHistone deacetylase inhibitionIDH1 mutant cellsGreater cell deathHDACi treatmentInhibitor vorinostatTumor xenograftsDeacetylase inhibitionIDH1/2 mutationsPotential biomarkersSpecific cancersMutant cancersCancerCancer cellsDNA repair defectsMalignancyVorinostatDNA double-strand breaksGliomasHistone hypermethylationCell deathPARPiA Benzenesulfonamide-based Mitochondrial Uncoupler Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Epithelial Ovarian Cancer
Bi F, Jiang Z, Park W, Hartwich TMP, Ge Z, Chong KY, Yang K, Morrison MJ, Kim D, Kim J, Zhang W, Kril LM, Watt DS, Liu C, Yang-Hartwich Y. A Benzenesulfonamide-based Mitochondrial Uncoupler Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Epithelial Ovarian Cancer. Molecular Cancer Therapeutics 2021, 20: molcanther.mct-21-0396-a.2021. PMID: 34625503, PMCID: PMC8643344, DOI: 10.1158/1535-7163.mct-21-0396.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerImmunogenic cell deathOvarian cancerTumor progressionAntitumor adaptive immune responsesDamage-associated molecular patternsCancer cellsMitochondrial uncouplerAdaptive immune responsesOvarian cancer modelCause of deathCurrent chemotherapeutic agentsNew therapeutic strategiesOvarian cancer cellsCancer cell proliferationCell deathEndoplasmic reticulum stressGynecologic malignanciesClinical outcomesEndoplasmic reticulum stress sensorNew anticancer therapiesPeritoneal fluidInduces Endoplasmic Reticulum StressImmune responseAbdominal cavityInhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function
Kumar M, Molkentine D, Molkentine J, Bridges K, Xie T, Yang L, Hefner A, Gao M, Bahri R, Dhawan A, Frederick MJ, Seth S, Abdelhakiem M, Beadle BM, Johnson F, Wang J, Shen L, Heffernan T, Sheth A, Ferris RL, Myers JN, Pickering CR, Skinner HD. Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function. Nature Communications 2021, 12: 6340. PMID: 34732714, PMCID: PMC8566594, DOI: 10.1038/s41467-021-26570-8.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsApoptosisBiomarkers, TumorBRCA1 ProteinCell Line, TumorCREB-Binding ProteinE1A-Associated p300 ProteinGain of Function MutationHistone AcetyltransferasesHomologous RecombinationHumansMaleMice, NudeMutationNeoplasmsProtein DomainsSquamous Cell Carcinoma of Head and NeckXenograft Model Antitumor AssaysPD-L1 (Programmed Death Ligand 1) Regulates T-Cell Differentiation to Control Adaptive Venous Remodeling
Matsubara Y, Gonzalez L, Kiwan G, Liu J, Langford J, Gao M, Gao X, Taniguchi R, Yatsula B, Furuyama T, Matsumoto T, Komori K, Mori M, Dardik A. PD-L1 (Programmed Death Ligand 1) Regulates T-Cell Differentiation to Control Adaptive Venous Remodeling. Arteriosclerosis Thrombosis And Vascular Biology 2021, 41: 2909-2922. PMID: 34670406, PMCID: PMC8664128, DOI: 10.1161/atvbaha.121.316380.Peer-Reviewed Original ResearchConceptsPD-L1AVF maturationPD-L1 activityVenous remodelingT cellsL1 antibodyArteriovenous fistulaNude miceMouse aortocaval fistula modelEnd-stage renal diseaseT helper type 2 cellsT helper type 1 (Th1) cellsPrimary success rateSmooth muscle cell proliferationRegulatory T cellsT cell activityT-cell transferAortocaval fistula modelPreferred vascular accessVascular wall thickeningM1-type macrophagesM2-type macrophagesPotential therapeutic targetMuscle cell proliferationType 1 cellsTargeting the Atf7ip–Setdb1 Complex Augments Antitumor Immunity by Boosting Tumor Immunogenicity
Hu H, Khodadadi-Jamayran A, Dolgalev I, Cho H, Badri S, Chiriboga LA, Zeck B, De Rodas Gregorio M, Dowling CM, Labbe K, Deng J, Chen T, Zhang H, Zappile P, Chen Z, Ueberheide B, Karatza A, Han H, Ranieri M, Tang S, Jour G, Osman I, Sucker A, Schadendorf D, Tsirigos A, Schalper KA, Velcheti V, Huang HY, Jin Y, Ji H, Poirier JT, Li F, Wong KK. Targeting the Atf7ip–Setdb1 Complex Augments Antitumor Immunity by Boosting Tumor Immunogenicity. Cancer Immunology Research 2021, 9: 1298-1315. PMID: 34462284, PMCID: PMC9414288, DOI: 10.1158/2326-6066.cir-21-0543.Peer-Reviewed Original ResearchConceptsHistone lysine methyltransferase 1Common adaptive mechanismSuppressor screenChromatin modifiersIntron retentionSET domainEpigenetic regulatorsEpigenetic modificationsEpigenetic modifiersType I interferon responseMethyltransferase 1I interferon responseHuman cancersTranscription factor 7Immune invasionInterferon responseAdaptive mechanismsFactor 7GenesCritical roleExpressionImmune evasionRejection of cellsAntigen processingAntigen expressionReprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy
Terranova C, Tang M, Maitituoheti M, Raman A, Ghosh A, Schulz J, Amin S, Orouji E, Tomczak K, Sarkar S, Oba J, Creasy C, Wu C, Khan S, Lazcano R, Wani K, Singh A, Barrodia P, Zhao D, Chen K, Haydu L, Wang W, Lazar A, Woodman S, Bernatchez C, Rai K. Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy. Cell Reports 2021, 36: 109410. PMID: 34289358, PMCID: PMC8369408, DOI: 10.1016/j.celrep.2021.109410.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationChromatinEnhancer of Zeste Homolog 2 ProteinFemaleGTP PhosphohydrolasesHistonesHumansMelanocytesMelanomaMembrane ProteinsMesodermMice, NudeMitogen-Activated Protein Kinase KinasesMutationNeoplasm MetastasisPolycomb Repressive Complex 2Transcription, GeneticTumor BurdenConceptsHistone H3 lysine 27 trimethylationH3 lysine 27 trimethylationBivalent chromatin stateCell identity genesLysine 27 trimethylationKey epigenetic alterationsNRAS mutantsMaster transcription factorBivalent domainsChromatin statePRC2 inhibitionEpigenetic elementsTranscription factorsEpigenetic alterationsGenetic driversMesenchymal phenotypeNRAS-mutant melanomaState profilingTherapeutic vulnerabilitiesInvasive capacityPharmacological inhibitionMutantsTherapeutic strategiesMelanoma samplesMutant melanoma patientsPhosphorylated WNK kinase networks in recoded bacteria recapitulate physiological function
Schiapparelli P, Pirman NL, Mohler K, Miranda-Herrera PA, Zarco N, Kilic O, Miller C, Shah SR, Rogulina S, Hungerford W, Abriola L, Hoyer D, Turk BE, Guerrero-Cázares H, Isaacs FJ, Quiñones-Hinojosa A, Levchenko A, Rinehart J. Phosphorylated WNK kinase networks in recoded bacteria recapitulate physiological function. Cell Reports 2021, 36: 109416. PMID: 34289367, PMCID: PMC8379681, DOI: 10.1016/j.celrep.2021.109416.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell Line, TumorCell MovementCell ProliferationEscherichia coliFemaleGlioblastomaHEK293 CellsHumansMaleMice, NudeMiddle AgedPhosphorylationPhosphoserineProtein Serine-Threonine KinasesRecombinant ProteinsSignal TransductionSmall Molecule LibrariesSubstrate SpecificityWNK Lysine-Deficient Protein Kinase 1ConceptsKinase networkAuthentic post-translational modificationsGenetic code expansionPost-translational modificationsProduction of proteinsSmall molecule kinase inhibitorsKinase inhibitorsGenetic codePhosphorylated proteinsCode expansionKinase proteinWNK kinasesPhysiological functionsWNK4 kinaseBiochemical propertiesGlioblastoma cellsKinaseBacterial strainsProteinDistinct sitesPhosphoserineSPAKBacteriaCellular systemsCellsLow doses of methylnaltrexone inhibits head and neck squamous cell carcinoma growth in vitro and in vivo by acting on the mu‐opioid receptor
Gorur A, Patiño M, Shi T, Corrales G, Takahashi H, Rangel R, Gleber‐Netto F, Pickering C, Myers JN, Cata JP. Low doses of methylnaltrexone inhibits head and neck squamous cell carcinoma growth in vitro and in vivo by acting on the mu‐opioid receptor. Journal Of Cellular Physiology 2021, 236: 7698-7710. PMID: 34038587, DOI: 10.1002/jcp.30421.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorCell MovementCell ProliferationEpithelial-Mesenchymal TransitionHead and Neck NeoplasmsHumansMaleMice, Inbred C57BLMice, NudeNaltrexoneNarcotic AntagonistsNeoplasm InvasivenessQuaternary Ammonium CompoundsReceptors, Opioid, muSignal TransductionSquamous Cell Carcinoma of Head and NeckTumor BurdenXenograft Model Antitumor AssaysConceptsMu-opioid receptorsEffects of methylnaltrexoneHNSCC cell linesTumor growthCell linesNeck squamous cell carcinoma growthNeck squamous cell carcinomaDifferent HNSCC cell linesClonogenic activitySquamous cell carcinoma growthSquamous cell carcinomaLung cancer cell linesCyclic adenosine monophosphate levelsTumor-bearing miceAggressive cell behaviorEpithelial-mesenchymal transitionAdenosine monophosphate levelsCancer cell linesCell carcinomaMethylnaltrexoneCarcinoma growthTherapeutic targetLow dosesFaDu cellsMetastasis formationMu-opioid receptor activation promotes in vitro and in vivo tumor growth in head and neck squamous cell carcinoma
Gorur A, Patiño M, Takahashi H, Corrales G, Pickering CR, Gleber-Netto FO, Myers JN, Cata JP. Mu-opioid receptor activation promotes in vitro and in vivo tumor growth in head and neck squamous cell carcinoma. Life Sciences 2021, 278: 119541. PMID: 33930368, DOI: 10.1016/j.lfs.2021.119541.Peer-Reviewed Original ResearchConceptsMu-opioid receptorsMOR activationTumor growthSelective MOR agonist DAMGOMu-opioid receptor activationNeck squamous cell carcinomaSquamous cell carcinoma progressionNeck squamous cell carcinoma progressionMOR agonist DAMGOSquamous cell carcinomaTumorigenesis of HNSCCPotential therapeutic targetVivo tumor growthAgonist DAMGOCell carcinomaSaline 0.9MOR agonistsTherapeutic targetCarcinoma progressionReceptor activationHNSCCVivo studiesColony formationCell linesMe-PheSTING enhances cell death through regulation of reactive oxygen species and DNA damage
Hayman TJ, Baro M, MacNeil T, Phoomak C, Aung TN, Cui W, Leach K, Iyer R, Challa S, Sandoval-Schaefer T, Burtness BA, Rimm DL, Contessa JN. STING enhances cell death through regulation of reactive oxygen species and DNA damage. Nature Communications 2021, 12: 2327. PMID: 33875663, PMCID: PMC8055995, DOI: 10.1038/s41467-021-22572-8.Peer-Reviewed Original ResearchHuman-Induced Pluripotent Stem-Cell-Derived Smooth Muscle Cells Increase Angiogenesis to Treat Hindlimb Ischemia
Gao X, Gao M, Gorecka J, Langford J, Liu J, Luo J, Taniguchi R, Matsubara Y, Liu H, Guo L, Gu Y, Qyang Y, Dardik A. Human-Induced Pluripotent Stem-Cell-Derived Smooth Muscle Cells Increase Angiogenesis to Treat Hindlimb Ischemia. Cells 2021, 10: 792. PMID: 33918299, PMCID: PMC8066461, DOI: 10.3390/cells10040792.Peer-Reviewed Original ResearchConceptsLimb-threatening ischemiaSmooth muscle cellsHindlimb ischemiaFunctional outcomeChronic limb-threatening ischemiaMuscle cellsVascular endothelial growth factor (VEGF) expressionM2-type macrophagesMurine hindlimb ischemia modelNumber of macrophagesGrowth factor expressionLaser Doppler imagingStem cell sourceHindlimb ischemia modelStem cellsConsiderable ethical issuesTranslatable therapyIschemic limbsRenewable stem cell sourcesIschemia modelCapillary densityBlood flowIschemiaNovel treatmentsNude miceCooperation between oncogenic Ras and wild-type p53 stimulates STAT non-cell autonomously to promote tumor radioresistance
Dong YL, Vadla GP, Lu J, Ahmad V, Klein TJ, Liu LF, Glazer PM, Xu T, Chabu CY. Cooperation between oncogenic Ras and wild-type p53 stimulates STAT non-cell autonomously to promote tumor radioresistance. Communications Biology 2021, 4: 374. PMID: 33742110, PMCID: PMC7979758, DOI: 10.1038/s42003-021-01898-5.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsAnimalsAnimals, Genetically ModifiedCell ProliferationCytokinesDrosophila melanogasterDrosophila ProteinsFemaleGene Expression Regulation, NeoplasticGenes, rasHumansJanus KinasesLung NeoplasmsMaleMice, NudeMice, TransgenicParacrine CommunicationRadiation ToleranceSignal TransductionSTAT Transcription FactorsTumor BurdenTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsTumor microenvironmentTumor radioresistanceRas clonesOncogenic Ras mutationsClinical outcomesRA tissuesCancer patientsJAK/STATRadiation therapyRobust tumorOncogenic RasTherapy outcomeTumor resistanceTumor tissueRas mutationsTumor cellsJAK/OutcomesRadioresistanceCellular responsesTissueCell-cell interactionsPatientsCytokinesRadiotherapy
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