2024
A first-in-human, phase 1/2 trial of FOG-001, a β-catenin:TCF antagonist, in patients with locally advanced or metastatic solid tumors.
Papadopoulos K, Rodon Ahnert J, Khushman M, Sharma S, Pelster M, Cecchini M, Kummar S, Choi M, Akella L, Garofalo A, Yu Z, Iyer V, Nguyen M, Orford K, Klempner S. A first-in-human, phase 1/2 trial of FOG-001, a β-catenin:TCF antagonist, in patients with locally advanced or metastatic solid tumors. Journal Of Clinical Oncology 2024, 42: tps3175-tps3175. DOI: 10.1200/jco.2024.42.16_suppl.tps3175.Peer-Reviewed Original ResearchNon-small cell lung cancerMSS colorectal cancerMetastatic solid tumorsSolid tumorsColorectal cancerAdenomatous polyposis coliT cell factorB-cateninAntitumor activityWnt/b-cateninPhase 1/2 trialCell lung cancerFirst-in-humanTumor growth inhibitionActivate oncogenic pathwaysIntravenous (IVWnt pathwayPathway activating mutationsWnt/b-catenin pathwayWnt pathway genesCurative chemoradiationDose escalationDose expansionGastric/GEJ cancerEscalating dosesWnt Signaling in Atherosclerosis: Mechanisms to Therapeutic Implications
Afroz R, Goodwin J. Wnt Signaling in Atherosclerosis: Mechanisms to Therapeutic Implications. Biomedicines 2024, 12: 276. PMID: 38397878, PMCID: PMC10886882, DOI: 10.3390/biomedicines12020276.Peer-Reviewed Original ResearchWnt pathwayWnt signalingAtherosclerosis progressionSmooth muscle cell proliferationMuscle cell proliferationPathophysiology of atherosclerosisBlock Wnt signalingDownstream signaling moleculesStages of atherosclerosis progressionPreclinical modelsMonocyte infiltrationEndothelial dysfunctionSmall molecule inhibitorsTreatment of atherosclerosisVascular inflammationTherapeutic approachesTherapeutic implicationsCo-receptorVascular diseaseAtherosclerosis developmentAtherosclerosisCell proliferationWnt ligandsMolecule inhibitorsWnt
2023
Endothelial Dysfunction in Cardiorenal Conditions: Implications of Endothelial Glucocorticoid Receptor-Wnt Signaling
Akhter M, Goodwin J. Endothelial Dysfunction in Cardiorenal Conditions: Implications of Endothelial Glucocorticoid Receptor-Wnt Signaling. International Journal Of Molecular Sciences 2023, 24: 14261. PMID: 37762564, PMCID: PMC10531724, DOI: 10.3390/ijms241814261.Peer-Reviewed Original ResearchConceptsGlucocorticoid receptorEndothelial dysfunctionVascular inflammationEndothelial cellsEndothelial glucocorticoid receptorAnti-inflammatory effectsFatty acid oxidation pathwayDifferent pathological conditionsSuppression of WntRenal diseaseInflammatory cascadeVascular toneNovel therapiesMultiple organsBlood fluidityEndothelial integrityPlatelet aggregationInnermost liningVessel permeabilityBlood vesselsPathological conditionsWnt pathwayInflammationDysfunctionDevastating diseaseDaam2 phosphorylation by CK2α negatively regulates Wnt activity during white matter development and injury
Wang C, Zuo Z, Jo J, Kim K, Madamba C, Ye Q, Jung S, Bellen H, Lee H. Daam2 phosphorylation by CK2α negatively regulates Wnt activity during white matter development and injury. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304112120. PMID: 37607236, PMCID: PMC10469030, DOI: 10.1073/pnas.2304112120.Peer-Reviewed Original ResearchConceptsOL developmentWhite matter injuryCentral nervous systemWnt/β-cateninWhite matter developmentWnt activityNeonatal hypoxiaBehavioral recoveryMyelin repairMyelin restorationNervous systemProtective roleOligodendrocyte developmentΒ-cateninWnt pathwayInjuryMyelinationBiological mechanismsNew biological mechanismsEarly differentiationPhosphorylationDemyelinationPathwayDisturbed flow increases endothelial inflammation and permeability via a Frizzled-4-β-catenin-dependent pathway
Rickman M, Ghim M, Pang K, von Huelsen Rocha A, Drudi E, Sureda-Vives M, Ayoub N, Tajadura-Ortega V, George S, Weinberg P, Warboys C. Disturbed flow increases endothelial inflammation and permeability via a Frizzled-4-β-catenin-dependent pathway. Journal Of Cell Science 2023, 136: jcs260449. PMID: 36846872, PMCID: PMC10112981, DOI: 10.1242/jcs.260449.Peer-Reviewed Original ResearchConceptsEndothelial dysfunctionEndothelial cellsFrizzled-4Β-cateninCultured human aortic endothelial cellsR-spondinsHuman aortic endothelial cellsPro-inflammatory genesEndothelial paracellular permeabilityDisturbed flowAortic endothelial cellsCultured endothelial cellsRole of WntEndothelial inflammationAortic archEarly atherogenesisCanonical Wnt pathwayDysfunctionReduced expressionWnt5a signalingParacellular permeabilityWnt pathwayInhibitionKnockdownExpression
2022
Pan-Cancer Single-Cell Analysis Reveals the Core Factors and Pathway in Specific Cancer Stem Cells of Upper Gastrointestinal Cancer
Li L, Zhang Y, Ren Y, Cheng Z, Zhang Y, Wang X, Zhao H, Lu H. Pan-Cancer Single-Cell Analysis Reveals the Core Factors and Pathway in Specific Cancer Stem Cells of Upper Gastrointestinal Cancer. Frontiers In Bioengineering And Biotechnology 2022, 10: 849798. PMID: 35646860, PMCID: PMC9136039, DOI: 10.3389/fbioe.2022.849798.Peer-Reviewed Original ResearchUpper gastrointestinal cancerCancer stem cellsPoor eating habitsTumor stem cellsChronic inflammationGastrointestinal cancerEating habitsStem cellsGastrointestinal cancer stem cellsPersistent chronic inflammationGastrointestinal cancer diagnosisCore signal pathwaysWnt pathway genesMucosa damagePoor outcomeAggressive carcinomasInflammatory genesSpecific cancer stem cellsCancer diagnosisCancerSignal pathwayInflammationWnt pathwayCell typesCells
2021
Wnt Signaling Cascades and Their Role in Coronary Artery Health and Disease
Weerackoon N, Gunawardhana KL, Mani A. Wnt Signaling Cascades and Their Role in Coronary Artery Health and Disease. Journal Of Cellular Signaling 2021, 2: 52-62. PMID: 33969358, PMCID: PMC8098721, DOI: 10.33696/signaling.2.035.Peer-Reviewed Original ResearchCoronary artery diseaseVascular smooth muscle cellsLow-density lipoproteinPlaque erosionDisease processWnt pathwayAdult cardiovascular diseaseDistinct disease processesSmooth muscle proliferationType 2 diabetesCause of deathMajor congenital defectsModified low-density lipoproteinSmooth muscle cellsWnt/β-catenin signalingCoronary artery healthCanonical Wnt/β-catenin signalingAggregation of monocytesActivation of WntΒ-catenin signalingArtery diseaseEndothelial cell defectsEndothelial dysfunctionWnt/CaVascular inflammationEXT1 methylation promotes proliferation and migration and predicts the clinical outcome of non‐small cell lung carcinoma via WNT signalling pathway
Kong W, Chen Y, Zhao Z, Zhang L, Lin X, Luo X, Wang S, Song Z, Lin X, Lai G, Yu Z. EXT1 methylation promotes proliferation and migration and predicts the clinical outcome of non‐small cell lung carcinoma via WNT signalling pathway. Journal Of Cellular And Molecular Medicine 2021, 25: 2609-2620. PMID: 33565239, PMCID: PMC7933929, DOI: 10.1111/jcmm.16277.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCarcinoma, Non-Small-Cell LungCell Line, TumorCell MovementCell ProliferationCpG IslandsDNA MethylationGene Expression Regulation, NeoplasticHumansLung NeoplasmsN-AcetylglucosaminyltransferasesNeoplasm GradingNeoplasm StagingPrognosisSurvival AnalysisWnt Signaling PathwayConceptsGene expressionGene body methylationDNA methylation levelsPotential downstream targetsDNA methylation sitesDNA methylationMethylation sitesDownstream targetsMethylation levelsWnt pathwayCpG sitesNSCLC cell linesMethylationWntExpression levelsCell linesPathway patternsPotential targetXAV-939EXT1ProliferationMigration ratePathwayExpressionUnderlying mechanism
2020
The role of Wnt signalling in development of coronary artery disease and its risk factors
Liu Y, Neogi A, Mani A. The role of Wnt signalling in development of coronary artery disease and its risk factors. Open Biology 2020, 10: 200128. PMID: 33081636, PMCID: PMC7653355, DOI: 10.1098/rsob.200128.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBiomarkersCarrier ProteinsCell DifferentiationCell MovementCoronary Artery DiseaseDisease SusceptibilityEndotheliumGene Expression RegulationHumansLipid MetabolismMacrophage ActivationMacrophagesMyocytes, Smooth MuscleProtein BindingRisk FactorsWnt ProteinsWnt Signaling PathwayConceptsCoronary artery diseaseArtery diseaseRole of WntVascular smooth muscle cellsEndothelial cell dysfunctionReduced blood flowLow-density lipoproteinModified low-density lipoproteinWnt pathwaySmooth muscle cellsNon-canonical Wnt/CaAggregation of monocytesTissue-resident macrophagesChest painEndothelial dysfunctionWnt/CaHeart failureLuminal narrowingCascade of eventsPathophysiological mechanismsMyocardial infarctionRisk factorsHeart diseaseCell dysfunctionInflammatory reactionTranscriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism
Breen MS, Browne A, Hoffman GE, Stathopoulos S, Brennand K, Buxbaum JD, Drapeau E. Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism. Molecular Autism 2020, 11: 53. PMID: 32560742, PMCID: PMC7304190, DOI: 10.1186/s13229-020-00355-0.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAutistic DisorderChildChild, PreschoolChromosome DeletionChromosome DisordersChromosomes, Human, Pair 22FemaleGene Expression ProfilingGene Expression RegulationHumansInduced Pluripotent Stem CellsMaleNeural Stem CellsNeuronsReproducibility of ResultsWnt Signaling PathwayConceptsNeural progenitor cellsTranscriptional signatureGene co-expression network analysisHiPSC-NPCsCo-expression network analysisIndependent biological samplesHiPSC-derived neural cellsProgenitor cellsPostsynaptic density genesDistinct transcriptional signaturesGenetic risk lociHuman-induced pluripotent stem cellsPluripotent stem cellsPotassium channel activityProtein translationSpecific neurobiological pathwaysTranscriptional differencesEmbryonic developmentLoss of SHANK3Risk lociHiPSC neuronsMorphological phenotypesWnt pathwayGenesHiPSC clonesEndothelial cell–glucocorticoid receptor interactions and regulation of Wnt signaling
Zhou H, Mehta S, Srivastava SP, Grabinska K, Zhang X, Wong C, Hedayat A, Perrotta P, Fernández-Hernando C, Sessa WC, Goodwin JE. Endothelial cell–glucocorticoid receptor interactions and regulation of Wnt signaling. JCI Insight 2020, 5: e131384. PMID: 32051336, DOI: 10.1172/jci.insight.131384.Peer-Reviewed Original ResearchConceptsEndothelial glucocorticoid receptorVascular inflammationGlucocorticoid receptorGlucocorticoid receptor regulationGlucocorticoid receptor resultsUpregulation of WntEndogenous glucocorticoidsExogenous glucocorticoidsGlucocorticoid response elementCardiovascular diseaseMouse endothelial cellsMouse modelEndothelial WNTInflammationReceptor regulationEndothelial cellsReceptors resultsNext-generation sequencingReceptor interactionReceptorsRegulation of WntWnt pathwayGlucocorticoidsRecent dataWnt
2019
Solid pseudopapillary neoplasms of the pancreas are dependent on the Wnt pathway
Selenica P, Raj N, Kumar R, Brown D, Arqués O, Reidy D, Klimstra D, Snuderl M, Serrano J, Palmer H, Weigelt B, Reis‐Filho J, Scaltriti M. Solid pseudopapillary neoplasms of the pancreas are dependent on the Wnt pathway. Molecular Oncology 2019, 13: 1684-1692. PMID: 30972907, PMCID: PMC6670010, DOI: 10.1002/1878-0261.12490.Peer-Reviewed Original ResearchConceptsSolid pseudopapillary neoplasmWnt pathwayLow‐complexity genomeWnt pathway genesPseudopapillary neoplasmSubtypes of pancreatic tumorsPrimary SPNPathway genesGenomic lesionsNuclear accumulationAdvanced stage diseaseEpithelial cell originSomatic mutationsWntGenomeMethylomeExpression levelsIndolent tumorsGenesPathwayPancreatic tumorsStage diseaseMutationsCell originClinical studiesGlobal gene expression of histologically normal primary skin cells from BCNS subjects reveals “single-hit” effects that are influenced by rapamycin
Phatak A, Athar M, Crowell JA, Leffel D, Herbert BS, Bale AE, Kopelovich L. Global gene expression of histologically normal primary skin cells from BCNS subjects reveals “single-hit” effects that are influenced by rapamycin. Oncotarget 2019, 10: 1360-1387. PMID: 30858923, PMCID: PMC6402716, DOI: 10.18632/oncotarget.26640.Peer-Reviewed Original ResearchGlobal gene expressionRapamycin treatmentGene expression changesGene expression profilingPresence of rapamycinBiomarkers/targetsExpression profilingGene expressionExpression changesPrimary cell culturesWnt pathwayCanonical HhGenesProbe setsMitochondrial dysfunctionStellate cell activationUnaffected skin biopsiesHeritable cancersPrimary skin cellsStem cellsRapamycinDevelopmental abnormalitiesDifferential responseGene signatureNormal fibroblastsAging-like Spontaneous Epigenetic Silencing Facilitates Wnt Activation, Stemness, and Braf V600E-Induced Tumorigenesis
Tao Y, Kang B, Petkovich DA, Bhandari YR, In J, Stein-O'Brien G, Kong X, Xie W, Zachos N, Maegawa S, Vaidya H, Brown S, Yen R, Shao X, Thakor J, Lu Z, Cai Y, Zhang Y, Mallona I, Peinado MA, Zahnow CA, Ahuja N, Fertig E, Issa JP, Baylin SB, Easwaran H. Aging-like Spontaneous Epigenetic Silencing Facilitates Wnt Activation, Stemness, and Braf V600E-Induced Tumorigenesis. Cancer Cell 2019, 35: 315-328.e6. PMID: 30753828, PMCID: PMC6636642, DOI: 10.1016/j.ccell.2019.01.005.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAge FactorsAgingAnimalsCell Transformation, NeoplasticColonic NeoplasmsDNA MethylationGene Expression Regulation, NeoplasticGene SilencingGenetic Predisposition to DiseaseHumansMice, Inbred NODMice, Mutant StrainsMice, SCIDMutationPhenotypeProto-Oncogene Proteins B-rafStem CellsTime FactorsTissue Culture TechniquesWnt Signaling PathwayConceptsCell fate changesPromoter DNA hypermethylationStem-like stateAging-like phenotypesCpG island methylationFate changesDifferentiation defectsEpigenetic abnormalitiesDNA hypermethylationSimultaneous inactivationWnt pathwayWnt activationPromoter hypermethylationTumorigenesisGenesHypermethylationMethylator phenotypeColon tumorigenesisPhenotypeOrganoidsPrecursor roleCRISPRMethylationSupStemness
2018
Impact of Transcriptomics on Our Understanding of Pulmonary Fibrosis
Vukmirovic M, Kaminski N. Impact of Transcriptomics on Our Understanding of Pulmonary Fibrosis. Frontiers In Medicine 2018, 5: 87. PMID: 29670881, PMCID: PMC5894436, DOI: 10.3389/fmed.2018.00087.Peer-Reviewed Original ResearchTranscriptomic studiesImpact of transcriptomicsGenome-scale profilingSingle-cell RNAseqRole of microRNAsIdiopathic pulmonary fibrosisNovel genesTranscriptomic analysisEpithelial genesIPF lungsRNA transcriptsDevelopmental pathwaysWnt pathwayBulk tissueMolecular analysisPulmonary fibrosisSpatial heterogeneityAnimal modelsTranscriptomicsGenesLethal fibrotic lung diseaseHuman IPF lungsImpact of lungPathwayFibrotic lung diseaseDKK2 imparts tumor immunity evasion through β-catenin-independent suppression of cytotoxic immune-cell activation
Xiao Q, Wu J, Wang WJ, Chen S, Zheng Y, Yu X, Meeth K, Sahraei M, Bothwell ALM, Chen L, Bosenberg M, Chen J, Sexl V, Sun L, Li L, Tang W, Wu D. DKK2 imparts tumor immunity evasion through β-catenin-independent suppression of cytotoxic immune-cell activation. Nature Medicine 2018, 24: 262-270. PMID: 29431745, PMCID: PMC5840007, DOI: 10.1038/nm.4496.Peer-Reviewed Original ResearchMeSH KeywordsAdenomatous Polyposis Coli Proteinbeta CateninCD8-Positive T-LymphocytesCell Line, TumorColorectal NeoplasmsCytotoxicity, ImmunologicGene Expression Regulation, NeoplasticHumansIntercellular Signaling Peptides and ProteinsIntestinal NeoplasmsKiller Cells, NaturalLow Density Lipoprotein Receptor-Related Protein-5MelanomaProgrammed Cell Death 1 ReceptorPTEN PhosphohydrolaseSignal TransductionSTAT5 Transcription FactorTumor EscapeDissecting Wnt Signaling for Melanocyte Regulation during Wound Healing
Sun Q, Rabbani P, Takeo M, Lee SH, Lim CH, Noel ES, Taketo MM, Myung P, Millar S, Ito M. Dissecting Wnt Signaling for Melanocyte Regulation during Wound Healing. Journal Of Investigative Dermatology 2018, 138: 1591-1600. PMID: 29428355, PMCID: PMC6019608, DOI: 10.1016/j.jid.2018.01.030.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCicatrixDisease Models, AnimalFemaleHumansIntercellular Signaling Peptides and ProteinsIntracellular Signaling Peptides and ProteinsKeratinocytesMaleMelanocytesMiceMice, TransgenicReceptors, G-Protein-CoupledRegenerationSkinSkin PigmentationStem CellsWnt ProteinsWnt Signaling PathwayWound HealingConceptsMelanocyte stem cellsMelanocyte regenerationEpidermal melanocytesStem cellsWnt ligand secretionActivation of WntWound healingSignal regulationEssential functionsWnt inhibitor Dkk1Wnt ligandsLigand secretionVital regulatorWnt pathwayTransgenic expressionWntMolecular windowΒ-cateninMelanocyte regulationInhibitor DKK1Epithelial cellsMelanocytesWound scarsRegulationAbnormal pigmentation
2017
Membrane-bound Dickkopf-1 in Foxp3+ regulatory T cells suppresses T cell-mediated autoimmune colitis
Chae W, Hao L, Henegariu O, Yilmaz S, Bothwell A. Membrane-bound Dickkopf-1 in Foxp3+ regulatory T cells suppresses T cell-mediated autoimmune colitis. The Journal Of Immunology 2017, 198: 156.8-156.8. DOI: 10.4049/jimmunol.198.supp.156.8.Peer-Reviewed Original ResearchDKK-1 expressionDickkopf-1T cellsImmunological toleranceT cell-mediated toleranceEffector CD4 T cellsT cell-mediated colitisRegulatory T cellsCD4 T cellsT cell receptor stimulationCell receptor stimulationActivated TregsAutoimmune colitisTreg markersColitis modelReceptor stimulationTregsCanonical Wnt pathwayDe novo protein synthesisCell proliferationColitisWnt pathwayNovo protein synthesisMAPK pathwayWnt ligands
2016
Liver serine palmitoyltransferase activity deficiency in early life impairs adherens junctions and promotes tumorigenesis
Li Z, Kabir I, Jiang H, Zhou H, Libien J, Zeng J, Stanek A, Ou P, Li KR, Zhang S, Bui HH, Kuo M, Park T, Kim B, Worgall TS, Huan C, Jiang X. Liver serine palmitoyltransferase activity deficiency in early life impairs adherens junctions and promotes tumorigenesis. Hepatology 2016, 64: 2089-2102. PMID: 27642075, PMCID: PMC5115983, DOI: 10.1002/hep.28845.Peer-Reviewed Original ResearchConceptsAdherens junctionsSerine palmitoyltransferaseHepatocyte polaritySubunit 2 geneCanonical Wnt pathwaySphingolipid biosynthesisPlasma membraneKey enzymeMajor proteinsWnt pathwayRecombination approachHepatocyte plasma membraneCellular distributionΒ-cateninTumorigenesisCadherin phosphorylationSphingomyelin levelsActivity deficiencyCentral componentPalmitoyltransferaseMembraneCadherinBiosynthesisLiver regenerationGenes
2014
Gene Expression in Relation to Exhaled Nitric Oxide Identifies Novel Asthma Phenotypes with Unique Biomolecular Pathways
Modena BD, Tedrow JR, Milosevic J, Bleecker ER, Meyers DA, Wu W, Bar-Joseph Z, Erzurum SC, Gaston BM, Busse WW, Jarjour NN, Kaminski N, Wenzel SE. Gene Expression in Relation to Exhaled Nitric Oxide Identifies Novel Asthma Phenotypes with Unique Biomolecular Pathways. American Journal Of Respiratory And Critical Care Medicine 2014, 190: 1363-1372. PMID: 25338189, PMCID: PMC4294630, DOI: 10.1164/rccm.201406-1099oc.Peer-Reviewed Original ResearchConceptsEpithelial cell gene expressionCell gene expressionGene expressionAirway epithelial cell gene expressionGene expression patternsSevere Asthma Research ProgramActin cytoskeletonGene clusterGenomic studiesGene transcriptionGene pathwaysMolecular basisExpression patternsAsthma phenotypesWnt pathwayMicroarray platformGenesNovel pathwayPhenotypeBiomolecular pathwaysNeuronal functionPathwayUnadjusted p-valuesExpressionBiological characteristics
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