2025
Interleukin-6 Trans Signaling Regulates Neutrophilic Inflammation in Alcohol-Associated Hepatitis
Sarode G, Hsu M, Haj F, Barace S, Argemi J, Liu M, Pandita P, Cao S, Shah V, Gui D, Bataller R, Rachakonda V. Interleukin-6 Trans Signaling Regulates Neutrophilic Inflammation in Alcohol-Associated Hepatitis. American Journal Of Pathology 2025 PMID: 40562277, DOI: 10.1016/j.ajpath.2025.05.023.Peer-Reviewed Original ResearchSTAT3-dependent gene expressionAlcohol-associated hepatitisSTAT3 activationIL-6 trans signalingRNA-seqTrans signalingIL-6R expressionGene expressionLiver RNA-seqIL-6Hyper-IL-6Neutrophilic inflammationIL-6 receptorIL-6RTGF-b1Intrahepatic neutrophil infiltrationLiver injury responsePathophysiology of AHTranscript enrichmentNegative regulatorChronic liver failureLiver disease patientsMembrane-boundSTAT3Severe AH
2024
The IL6/JAK/STAT3 signaling axis is a therapeutic vulnerability in SMARCB1-deficient bladder cancer
Amara C, Kami Reddy K, Yuntao Y, Chan Y, Piyarathna D, Dobrolecki L, Shih D, Shi Z, Xu J, Huang S, Ellis M, Apolo A, Ballester L, Gao J, Hansel D, Lotan Y, Hodges H, Lerner S, Creighton C, Sreekumar A, Zheng W, Msaouel P, Kavuri S, Putluri N. The IL6/JAK/STAT3 signaling axis is a therapeutic vulnerability in SMARCB1-deficient bladder cancer. Nature Communications 2024, 15: 1373. PMID: 38355560, PMCID: PMC10867091, DOI: 10.1038/s41467-024-45132-2.Peer-Reviewed Original ResearchConceptsSignaling AxisSMARCB1-deficient tumorsSMARCB1 deficiencyBladder cancerChromatin accessibilitySTAT3 inhibitorTumor growthSMARCB1 lossPatient-derived xenograft modelsCell line-derived xenograftsTherapeutic vulnerabilitiesTarget pathwaysReduced tumor growthIncreased tumor growthCell linesIn vivo modelsSTAT3Gene signatureSMARCB1TTI-101Solid tumorsXenograft modelClinical evaluationDisease progressionTumor
2021
Targeting STAT3 prevents bile reflux‐induced oncogenic molecular events linked to hypopharyngeal carcinogenesis
Vageli DP, Doukas PG, Siametis A, Judson BL. Targeting STAT3 prevents bile reflux‐induced oncogenic molecular events linked to hypopharyngeal carcinogenesis. Journal Of Cellular And Molecular Medicine 2021, 26: 75-87. PMID: 34850540, PMCID: PMC8742186, DOI: 10.1111/jcmm.17011.Peer-Reviewed Original ResearchConceptsBcl-2 overexpressionTranscriptional activationTranscription factorsTranscriptional activitySignal transducerSTAT3 knockdownMolecular eventsCell survivalQPCR analysisLuciferase assaySTAT3 activationTargeting STAT3Oncogenic eventsAberrant activationHypopharyngeal carcinogenesisSTAT3 phosphorylationSTAT3Oncogenic effectsSTAT3 pathwayPharmacologic inhibitionPharmacological inhibitionSTA-21Hypopharyngeal cellsOncogenic profileWestern blotYAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation
He L, Pratt H, Gao M, Wei F, Weng Z, Struhl K. YAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation. ELife 2021, 10: e67312. PMID: 34463254, PMCID: PMC8463077, DOI: 10.7554/elife.67312.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingCell Line, TumorCell Transformation, NeoplasticDatabases, GeneticFemaleGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsProtein BindingProtein Interaction Domains and MotifsSignal TransductionSTAT3 Transcription FactorTranscription Factor AP-1Transcription FactorsTranscriptional ActivationTranscriptional Coactivator with PDZ-Binding Motif ProteinsTriple Negative Breast NeoplasmsYAP-Signaling ProteinsConceptsTranscriptional co-activatorAP-1 proteinsAP-1Cellular transformationTarget siteNon-overlapping genesStimulated transcriptional activityAssociated with poor survival of breast cancer patientsPoor survival of breast cancer patientsSTAT3 motifTEAD proteinsSequence motifsGene classesWW domainEpigenetic switchTaz paralogTAZ-specificTranscriptional activityTranscription factorsTEADYAP/TAZSTAT3MotifTAZJunBSTAT3 polymorphisms in North Africa and its implication in breast cancer
Ziadi W, Boussetta S, Elkamel S, Pakstis AJ, Kidd KK, Medimegh I, Elgaaied A, Cherni L. STAT3 polymorphisms in North Africa and its implication in breast cancer. Molecular Genetics & Genomic Medicine 2021, 9: e1744. PMID: 34251094, PMCID: PMC8404238, DOI: 10.1002/mgg3.1744.Peer-Reviewed Original ResearchConceptsNorth African populationsAfrican populationsSTAT3 regionSingle nucleotide polymorphismsRare haplotypesHsa-mirMiR databaseMajor haplotypesGenesNucleotide polymorphismsHaplotypesSNPsSTAT3Allele frequenciesRs7211777Tunisian populationPolymorphismPopulationDiversityNorth AfricaAllelesSignificant frequencyRecombinationAssaysCancer
2020
IL6/STAT3 Signaling Hijacks Estrogen Receptor α Enhancers to Drive Breast Cancer Metastasis
Siersbæk R, Scabia V, Nagarajan S, Chernukhin I, Papachristou E, Broome R, Johnston S, Joosten S, Green A, Kumar S, Jones J, Omarjee S, Alvarez-Fernandez R, Glont S, Aitken S, Kishore K, Cheeseman D, Rakha E, D'Santos C, Zwart W, Russell A, Brisken C, Carroll J. IL6/STAT3 Signaling Hijacks Estrogen Receptor α Enhancers to Drive Breast Cancer Metastasis. Cancer Cell 2020, 38: 412-423.e9. PMID: 32679107, PMCID: PMC7116707, DOI: 10.1016/j.ccell.2020.06.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, HormonalBreast NeoplasmsEnhancer Elements, GeneticEstrogen Receptor alphaFemaleFulvestrantGene Expression ProfilingGene Expression Regulation, NeoplasticHumansInterleukin-6Kaplan-Meier EstimateMCF-7 CellsMice, Inbred NODMice, KnockoutMice, SCIDNeoplasm MetastasisSignal TransductionSTAT3 Transcription FactorXenograft Model Antitumor AssaysConceptsEstrogen receptor aInhibition of STAT3 activationOncogenic pathwaysBreast cancer invasionSTAT3 activationTranscriptional programsDownstream effector STAT3STAT3IL6/STAT3 signalingIndependent of ERCancer invasionER enhancementER-targeted therapiesBreast cancerCytokine interleukin-6Interleukin-6PathwayIL6/STAT3Receptor AMacrophages Promote Aortic Valve Cell Calcification and Alter STAT3 Splicing
Raddatz M, Huffstater T, Bersi M, Reinfeld B, Madden M, Booton S, Rathmell W, Rathmell J, Lindman B, Madhur M, Merryman W. Macrophages Promote Aortic Valve Cell Calcification and Alter STAT3 Splicing. Arteriosclerosis Thrombosis And Vascular Biology 2020, 40: e153-e165. PMID: 32295422, PMCID: PMC7285853, DOI: 10.1161/atvbaha.120.314360.Peer-Reviewed Original ResearchConceptsValve cellsMurine aortic valvesAortic valve diseaseCalcific aortic valve diseaseBone marrow genotypeOsteogenic calcificationAortic valve cellsMacrophage-driven inflammationValve diseaseMacrophage maturationMacrophage recruitmentMacrophage interactionsCell secretionCell calcificationAortic valveTherapeutic targetSTAT3Flow cytometryExpression of MHCIIMaturationBone marrow transplantRecruitmentGenotypesMacrophagesCells
2018
Science to Practice: Decrypting the Enigma of Ablation-induced Off-Target Effects-Is Network Pathway Analysis the Final Piece of the Puzzle?
Murali N, Laage-Gaupp FM, Chapiro J, Geschwind JF. Science to Practice: Decrypting the Enigma of Ablation-induced Off-Target Effects-Is Network Pathway Analysis the Final Piece of the Puzzle? Radiology 2018, 286: 405-408. PMID: 29356646, DOI: 10.1148/radiol.2017171779.Peer-Reviewed Original Research
2017
Colony Lysate Arrays for Proteomic Profiling of Drug-Tolerant Persisters of Cancer Cell
Kume K, Nishizuka SS. Colony Lysate Arrays for Proteomic Profiling of Drug-Tolerant Persisters of Cancer Cell. Analytical Chemistry 2017, 89: 8626-8631. PMID: 28753272, DOI: 10.1021/acs.analchem.7b01215.Peer-Reviewed Original ResearchConceptsDrug-tolerant persistersCancer cellsTranscription factorsProteomic profilingProteomic profilesLevels of proteinIndividual coloniesProtein array systemNumber of assaysSingle cellsProtein levelsCritical mechanismFunctional informationAlternative therapeutic targetsProteinTherapeutic targetFunctional heterogeneityCellsInitiation of relapseProfilingPersistersAgarose gelOct4ASTAT3ColoniesHuman CD39+ Treg Cells Express Th17-Associated Surface Markers and Suppress IL-17 via a Stat3-Dependent Mechanism
Magid-Bernstein JR, Rohowsky-Kochan CM. Human CD39+ Treg Cells Express Th17-Associated Surface Markers and Suppress IL-17 via a Stat3-Dependent Mechanism. Journal Of Interferon & Cytokine Research 2017, 37: 153-164. PMID: 28387597, PMCID: PMC6435349, DOI: 10.1089/jir.2016.0071.Peer-Reviewed Original ResearchConceptsIL-17STAT3-dependent mechanismIL-23RHuman CD4T effector cellsIFN-γ productionEctonucleotidase CD39Autologous CD4Regulatory cellsAutoimmune responseEffector cellsAutoimmune diseasesTranscription factor STAT3Immune responseProliferative responseCD25CD4CD39Human CD39Surface markersSTAT3 activationCCR6STAT3CellsFirst evidence
2016
miR-182-5p Induced by STAT3 Activation Promotes Glioma Tumorigenesis
Xue J, Zhou A, Wu Y, Morris S, Lin K, Amin S, Verhaak R, Fuller G, Xie K, Heimberger A, Huang S. miR-182-5p Induced by STAT3 Activation Promotes Glioma Tumorigenesis. Cancer Research 2016, 76: 4293-4304. PMID: 27246830, PMCID: PMC5033679, DOI: 10.1158/0008-5472.can-15-3073.Peer-Reviewed Original ResearchConceptsProtocadherin-8Glioma tumorigenesisProtein-coding genesMiRNA gene transcriptionCandidate target genesExpression of STAT3Gene transcriptionBioinformatics analysisTarget genesSTAT3/miRSTAT3 knockdownPCDH8 expressionSTAT3 inhibitorAberrant activationGlioblastoma tissuesSTAT3Expression levelsInvasive capacityTranscriptionTumorigenesisGlioma progressionGenesCritical roleKnockdownP-STAT3
2013
STAT3 expression, activity and functional consequences of STAT3 inhibition in esophageal squamous cell carcinomas and Barrett’s adenocarcinomas
Timme S, Ihde S, Fichter C, Waehle V, Bogatyreva L, Atanasov K, Kohler I, Schöpflin A, Geddert H, Faller G, Klimstra D, Tang L, Reinheckel T, Hauschke D, Busch H, Boerries M, Werner M, Lassmann S. STAT3 expression, activity and functional consequences of STAT3 inhibition in esophageal squamous cell carcinomas and Barrett’s adenocarcinomas. Oncogene 2013, 33: 3256-3266. PMID: 23912451, DOI: 10.1038/onc.2013.298.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaBarrett EsophagusCarcinoma, Squamous CellCell CycleCell Growth ProcessesCell Line, TumorCell MovementDown-RegulationEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaGene Knockdown TechniquesHumansPhosphorylationSignal TransductionSTAT3 Transcription FactorUp-RegulationConceptsSTAT3 knockdownSTAT3 expressionCell migrationEpidermal growth factorSTAT3 activationSTAT3-regulated genesP-STAT3STAT3 Tyr705 phosphorylationOE33 cellsOE21 cellsCell cycle genesActive p-Stat3Migration of ESCC cellsBAC cellsCell proliferationSTAT3 Tyr705Cell motilityEsophageal squamous cell carcinomaTherapeutic targetCycle genesReduced cell proliferationCellular functionsSignal transducerSTAT3 inhibitionSTAT3Inhibition of Signal Transducer and Activator of Transcription 3 and Cyclooxygenase-2 Is Involved in Radiosensitization of Cepharanthine in HeLa Cells
Fang Z, Li Y, Chen Z, Wang J, Zhu L. Inhibition of Signal Transducer and Activator of Transcription 3 and Cyclooxygenase-2 Is Involved in Radiosensitization of Cepharanthine in HeLa Cells. International Journal Of Gynecological Cancer 2013, 23: 608-614. PMID: 23466568, DOI: 10.1097/igc.0b013e31828a05fd.Peer-Reviewed Original ResearchConceptsHeLa cellsSignal transducerTranscription 3C-MycSTAT3 target genesCell cycle regulators c-MycBcl-2Antiapoptotic Bcl-2Target genesWestern blot analysisHeLa cell lineApoptosis inductionBlot analysisNude mouse xenograftsCell linesReduced expressionSTAT3Apoptosis analysisMouse xenograftsSignificant radiosensitizationIR treatmentClonogenic assayActivatorCellsCytotoxic effects
2012
First-in-Human Trial of a STAT3 Decoy Oligonucleotide in Head and Neck Tumors: Implications for Cancer Therapy
Sen M, Thomas SM, Kim S, Yeh JI, Ferris RL, Johnson JT, Duvvuri U, Lee J, Sahu N, Joyce S, Freilino ML, Shi H, Li C, Ly D, Rapireddy S, Etter JP, Li PK, Wang L, Chiosea S, Seethala RR, Gooding WE, Chen X, Kaminski N, Pandit K, Johnson DE, Grandis JR. First-in-Human Trial of a STAT3 Decoy Oligonucleotide in Head and Neck Tumors: Implications for Cancer Therapy. Cancer Discovery 2012, 2: 694-705. PMID: 22719020, PMCID: PMC3668699, DOI: 10.1158/2159-8290.cd-12-0191.Peer-Reviewed Original ResearchConceptsSTAT3 target genesTarget genesSTAT3 target gene expressionSTAT3-selective inhibitorsTarget gene expressionInhibited xenograft growthSelective STAT3 inhibitorSystemic administrationTranscription factor decoyTranscription factorsSTAT3 proteinBroader clinical developmentGene expressionPhase 0 trialsSTAT3 inhibitorHuman cancersSTAT3Expression levelsSTAT3 decoyCancer cellsCellular viabilityNeck cancerSaline controlsNeck tumorsHuman trials
2011
An Interleukin-21- Interleukin-10-STAT3 Pathway Is Critical for Functional Maturation of Memory CD8+ T Cells
Cui W, Liu Y, Weinstein JS, Craft J, Kaech SM. An Interleukin-21- Interleukin-10-STAT3 Pathway Is Critical for Functional Maturation of Memory CD8+ T Cells. Immunity 2011, 35: 792-805. PMID: 22118527, PMCID: PMC3431922, DOI: 10.1016/j.immuni.2011.09.017.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationGene Expression Regulation, DevelopmentalImmunologic MemoryInterleukin-10InterleukinsMiceMice, KnockoutPositive Regulatory Domain I-Binding Factor 1Proto-Oncogene Proteins c-bcl-6Signal TransductionSTAT3 Transcription FactorSuppressor of Cytokine Signaling 3 ProteinSuppressor of Cytokine Signaling ProteinsT-Box Domain ProteinsTranscription FactorsConceptsMemory T cellsT cellsBCL-6Protective memory T cellsCentral memory T cellsSTAT3 pathwayAcute LCMV infectionExpression of EomesLong-term immunityMemory precursor cellsSTAT3-SOCS3 pathwayMemory cell developmentCell developmentT cell developmentMemory CD8IL-21LCMV infectionIL-12Interleukin-10Inflammatory cytokinesFunctional maturationSOCS3 expressionBlimp-1Precursor cellsSTAT3
2010
Genome-wide Association Study in a High-Risk Isolate for Multiple Sclerosis Reveals Associated Variants in STAT3 Gene
Jakkula E, Leppä V, Sulonen AM, Varilo T, Kallio S, Kemppinen A, Purcell S, Koivisto K, Tienari P, Sumelahti ML, Elovaara I, Pirttilä T, Reunanen M, Aromaa A, Oturai AB, Søndergaard HB, Harbo HF, Mero IL, Gabriel SB, Mirel DB, Hauser SL, Kappos L, Polman C, De Jager PL, Hafler DA, Daly MJ, Palotie A, Saarela J, Peltonen L. Genome-wide Association Study in a High-Risk Isolate for Multiple Sclerosis Reveals Associated Variants in STAT3 Gene. American Journal Of Human Genetics 2010, 86: 285-291. PMID: 20159113, PMCID: PMC2820168, DOI: 10.1016/j.ajhg.2010.01.017.Peer-Reviewed Original ResearchConceptsSTAT3 geneGenome-wide association studiesRare risk allelesComplex traitsRisk lociRisk allelesAssociated variantsAssociation studiesRecent GWASInternal isolateLociCommon variantsGenetic riskGenesAllelesCritical roleSTAT3Small odds ratiosHeterogeneous populationVariantsGWASIsolatesProtective haplotypeTraitsSNPs
2009
STAT3 inhibition of gluconeogenesis is downregulated by SirT1
Nie Y, Erion DM, Yuan Z, Dietrich M, Shulman GI, Horvath TL, Gao Q. STAT3 inhibition of gluconeogenesis is downregulated by SirT1. Nature Cell Biology 2009, 11: 492-500. PMID: 19295512, PMCID: PMC2790597, DOI: 10.1038/ncb1857.Peer-Reviewed Original Research
2004
Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation
Gao Q, Wolfgang MJ, Neschen S, Morino K, Horvath TL, Shulman GI, Fu XY. Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 4661-4666. PMID: 15070774, PMCID: PMC384803, DOI: 10.1073/pnas.0303992101.Peer-Reviewed Original ResearchMeSH KeywordsAcute-Phase ProteinsAdipose Tissue, BrownAnimalsBody Temperature RegulationCorticosteroneDiabetes MellitusDNA-Binding ProteinsFemaleInfertility, FemaleInfertility, MaleIntermediate Filament ProteinsKineticsLeptinMaleMiceMice, KnockoutMice, TransgenicNerve Tissue ProteinsNestinObesityRatsSTAT3 Transcription FactorTime FactorsTrans-ActivatorsConceptsSignal transducerActivator of transcriptionApparent developmental abnormalitiesEnergy homeostasisGenetic modelsTranscription 3Mendelian ratioHomozygous mutantsCold stressNeonatal lethalityPhysiological roleMutantsGlial differentiationUnique phenotypeSTAT3Essential roleDevelopmental abnormalitiesHomeostasisActivatorNeuroendocrine defectsTranscriptionDisruptionProteinKnockoutReproduction
2003
STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: A critical role of STAT3 in innate immunity
Welte T, Zhang SS, Wang T, Zhang Z, Hesslein DG, Yin Z, Kano A, Iwamoto Y, Li E, Craft JE, Bothwell AL, Fikrig E, Koni PA, Flavell RA, Fu XY. STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: A critical role of STAT3 in innate immunity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 1879-1884. PMID: 12571365, PMCID: PMC149927, DOI: 10.1073/pnas.0237137100.Peer-Reviewed Original ResearchConceptsDeletion of Stat3STAT3 deletionInnate immune responseKey transcriptional mediatorNormal embryonic developmentCell-autonomous proliferationAbsence of STAT3Tissue-specific disruptionImmune responseInnate immunityCritical roleTumor necrosis factor alphaNF-kappa B activationTranscriptional mediatorsEmbryonic developmentBowel wall thickeningHematopoiesis resultsInflammatory cell infiltrationSignal transducerNecrosis factor alphaTranscription 3NAPDH oxidase activityBone marrow cellsMyeloid lineageSTAT3
2001
Defining a molecular fingerprint of STAT3-regulated genes associated with oncogenesis using microarray technology and novel statistical methods
Sinibaldi D, Garcia R, Bloom G, Mane S, Geiser P, Minton S, Muro-Cacho C, Lazaridis E, Jove R. Defining a molecular fingerprint of STAT3-regulated genes associated with oncogenesis using microarray technology and novel statistical methods. Nature Genetics 2001, 27: 86-86. DOI: 10.1038/87296.Peer-Reviewed Original Research
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