2023
Daam2 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 differentiationPhosphorylationDemyelinationPathway
2022
The origins of skin diversity: lessons from dermal fibroblasts
Myung P, Andl T, Atit R. The origins of skin diversity: lessons from dermal fibroblasts. Development 2022, 149 PMID: 36444877, PMCID: PMC10112899, DOI: 10.1242/dev.200298.Peer-Reviewed Original ResearchConceptsFibroblast subtypesSingle-cell levelWnt/β-cateninLineage diversificationHair follicle growthDermal developmentDermal fibroblastsExtraordinary diversityPositional signalsNatural variationFibroblast heterogeneityΒ-cateninDevelopmental originsDiverse groupMolecular heterogeneityCentral roleDiversityFibroblastsFollicle growthImportant roleLineagesSpeciesDiversificationDifferentiationOriginHistone H3 proline 16 hydroxylation regulates mammalian gene expression
Liu X, Wang J, Boyer J, Gong W, Zhao S, Xie L, Wu Q, Zhang C, Jain K, Guo Y, Rodriguez J, Li M, Uryu H, Liao C, Hu L, Zhou J, Shi X, Tsai Y, Yan Q, Luo W, Chen X, Strahl B, von Kriegsheim A, Zhang Q, Wang G, Baldwin A, Zhang Q. Histone H3 proline 16 hydroxylation regulates mammalian gene expression. Nature Genetics 2022, 54: 1721-1735. PMID: 36347944, PMCID: PMC9674084, DOI: 10.1038/s41588-022-01212-x.Peer-Reviewed Original ResearchConceptsPost-translational modificationsHistone post-translational modificationsMammalian gene expressionGene expressionHistone H3Mammalian cellsDNA-templated processesTranscriptome-wide analysisTarget gene expressionHydroxylation of prolineWnt/β-cateninChromatin recruitmentHistone codeTarget genesRegulatory marksLysine residuesDirect bindingTriple-negative breast cancerΒ-cateninResidues 16H3ExpressionH3K4me3TrimethylationGenomeDecomposing a deterministic path to mesenchymal niche formation by two intersecting morphogen gradients
Qu R, Gupta K, Dong D, Jiang Y, Landa B, Saez C, Strickland G, Levinsohn J, Weng PL, Taketo MM, Kluger Y, Myung P. Decomposing a deterministic path to mesenchymal niche formation by two intersecting morphogen gradients. Developmental Cell 2022, 57: 1053-1067.e5. PMID: 35421372, PMCID: PMC9050909, DOI: 10.1016/j.devcel.2022.03.011.Peer-Reviewed Original ResearchConceptsMorphogen gradientsCell fate specificationWnt/β-cateninFate specificationShape tissuesOrgan formationCell fateDermal condensatesGenetic perturbationsNiche formationDifferentiation processSpatiotemporal patterningCell behaviorΒ-cateninMore intermediatesComputational approachProliferationMorphogenesisScRNAOrganogenesisShhKey componentProgenitorsCritical transitionDKK1Predictive Markers of Response to Neoadjuvant Durvalumab with Nab-Paclitaxel and Dose-Dense Doxorubicin/Cyclophosphamide in Basal-Like Triple-Negative Breast Cancer.
Blenman KRM, Marczyk M, Karn T, Qing T, Li X, Gunasekharan V, Yaghoobi V, Bai Y, Ibrahim EY, Park T, Silber A, Wolf DM, Reisenbichler E, Denkert C, Sinn BV, Rozenblit M, Foldi J, Rimm DL, Loibl S, Pusztai L. Predictive Markers of Response to Neoadjuvant Durvalumab with Nab-Paclitaxel and Dose-Dense Doxorubicin/Cyclophosphamide in Basal-Like Triple-Negative Breast Cancer. Clinical Cancer Research 2022, 28: 2587-2597. PMID: 35377948, PMCID: PMC9464605, DOI: 10.1158/1078-0432.ccr-21-3215.Peer-Reviewed Original ResearchConceptsBasal-like triple-negative breast cancerPathologic complete responseResidual diseaseNeoadjuvant durvalumabDNA damage repairSomatic mutationsBreast cancerWnt/β-cateninHigh expressionTriple-negative breast cancerBasal-Like TripleDoxorubicin/cyclophosphamideDNA repairTumor mutation burdenRNA sequencingEpithelial-mesenchymal transitionFive-gene signatureB-cell markersCancer driversEnrichment analysisNegative breast cancerDamage repairGene expressionJAK-STATCell cycle
2021
PIK3CA mutation in a case of CTNNB1 mutant sinonasal glomangiopericytoma
Hong C, Khan M, Sukys J, Prasad M, Erson-Omay EZ, Vining E, Omay SB. PIK3CA mutation in a case of CTNNB1 mutant sinonasal glomangiopericytoma. Molecular Case Studies 2021, 8: mcs.a006120. PMID: 34667073, PMCID: PMC8744496, DOI: 10.1101/mcs.a006120.Peer-Reviewed Original ResearchConceptsCase of glomangiopericytomaWhole-exome sequencingInstitutional review board-approved protocolTargeted medical therapyUnderwent surgical resectionPI3K/Akt/mTORWnt/β-cateninAkt/mTORPrimary sinonasal tumorSurgical resectionClinicopathologic characteristicsMedical therapyRare tumorPIK3CA mutationsSinonasal tumorsGlomangiopericytomaTumorsΒ-cateninSomatic mutationsComprehensive genetic characterizationGenomic characterizationMutationsConcurrent dysregulationResectionSinonasalMolecular correlates of response to nivolumab at baseline and on treatment in patients with RCC
Ross-Macdonald P, Walsh AM, Chasalow SD, Ammar R, Papillon-Cavanagh S, Szabo PM, Choueiri TK, Sznol M, Wind-Rotolo M. Molecular correlates of response to nivolumab at baseline and on treatment in patients with RCC. Journal For ImmunoTherapy Of Cancer 2021, 9: e001506. PMID: 33658305, PMCID: PMC7931766, DOI: 10.1136/jitc-2020-001506.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorCarcinoma, Renal CellCD4 AntigensCD8 AntigensCytokinesDrug Resistance, NeoplasmHumansImmune Checkpoint InhibitorsKidney NeoplasmsLymphocytes, Tumor-InfiltratingMutationNivolumabProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-CellT-LymphocytesTime FactorsTreatment OutcomeConceptsClear cell renal cell carcinomaMetastatic clear cell renal cell carcinomaT cell infiltrationNivolumab responseExact testDeath ligand 1 (PD-L1) statusFirst-line treatment decisionsT-cell receptor clonalitySerum cytokine assaysImmune checkpoint inhibitorsNon-responding patientsDeath-1 receptorCell renal cell carcinomaSubset of patientsRenal cell carcinomaFisher's exact testWnt/β-cateninLogistic regression modelsRank sum testCD8 statusCheckpoint inhibitorsIndex lesionPatient selectionTCR clonalityCell carcinoma
2020
Re-appraising the potential of naringin for natural, novel orthopedic biotherapies
Yu KE, Alder KD, Morris MT, Munger AM, Lee I, Cahill SV, Kwon HK, Back J, Lee FY. Re-appraising the potential of naringin for natural, novel orthopedic biotherapies. Therapeutic Advances In Musculoskeletal Disease 2020, 12: 1759720x20966135. PMID: 33343723, PMCID: PMC7727086, DOI: 10.1177/1759720x20966135.Peer-Reviewed Original ResearchBone morphogenetic proteinExtracellular signal-related kinase (ERK) pathwayRANK/RANKL interactionNumerous molecular pathwaysWnt/β-cateninBone resident cellsStem cell precursorsCellular differentiationKinase pathwayMorphogenetic proteinsPotential of naringinMolecular pathwaysΒ-cateninCellular mechanismsBone-preserving effectCommon musculoskeletal pathologiesEstrogen-sensitive tissuesOsteolytic bone diseaseCommon musculoskeletal conditionsMusculoskeletal developmentSystemic side effectsTreatment of osteoporosisDegenerative joint diseaseCell precursorsBone microenvironment
2019
Lgr5 Functions As a Critical Negative Regulator of Wnt/β-Catenin Signaling and Is Essential for B-Lymphopoiesis and Malignant B-Cell Transformation
Cosgun K, Deb G, Yang X, Xiao G, Sadras T, Lee J, Chan L, Kume K, Yang L, Geng H, Chan J, Song J, Jumaa H, Polson A, Clevers H, Müschen M. Lgr5 Functions As a Critical Negative Regulator of Wnt/β-Catenin Signaling and Is Essential for B-Lymphopoiesis and Malignant B-Cell Transformation. Blood 2019, 134: 748. DOI: 10.1182/blood-2019-127263.Peer-Reviewed Original ResearchB-cell lineage acute lymphoblastic leukemiaWnt/β-catenin signalingΒ-catenin signalingNuclear β-cateninAntibody-drug conjugatesB cell developmentB cell survivalΒ-cateninB lymphopoiesisFunction of LGR5Median mRNA levelsTime of diagnosisPoor clinical outcomeRole of LGR5Acute lymphoblastic leukemiaB-cell lymphomaLeukemia initiating cellsWnt/β-cateninHigh surface expressionMalignant B-cell transformationCell linesB cell precursorsTypes of cancerHuman colon cancer cell linesB-cell lineage
2018
Valproic Acid Inhibits Proliferation and Reduces Invasiveness in Glioma Stem Cells Through Wnt/β Catenin Signalling Activation
Riva G, Cilibrasi C, Bazzoni R, Cadamuro M, Negroni C, Butta V, Strazzabosco M, Dalprà L, Lavitrano M, Bentivegna A. Valproic Acid Inhibits Proliferation and Reduces Invasiveness in Glioma Stem Cells Through Wnt/β Catenin Signalling Activation. Genes 2018, 9: 522. PMID: 30373123, PMCID: PMC6267016, DOI: 10.3390/genes9110522.Peer-Reviewed Original ResearchGSC proliferationMethylation changesBioinformatics analysisGenome-wide dataStem cellsWnt/β-catenin signalingCell-signaling pathwaysWnt/β-catenin signaling activationWnt/β-cateninValproic acidΒ-catenin signalingVPA effectsHistone deacetylase inhibitorsGlioma stem cellsTrypan blue assayReal-time PCRLuciferase reporterN-cadherinSignaling ActivationPleiotropic effectsAnti-cancer effectsΒ-cateninE-cadherinCommon malignant brain tumorGSC invasionmiR-221/222 activate the Wnt/β-catenin signaling to promote triple-negative breast cancer
Liu S, Wang Z, Liu Z, Shi S, Zhang Z, Zhang J, Lin H. miR-221/222 activate the Wnt/β-catenin signaling to promote triple-negative breast cancer. Journal Of Molecular Cell Biology 2018, 10: 302-315. PMID: 30053090, DOI: 10.1093/jmcb/mjy041.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerWnt/β-cateninMiR-221/222 expressionTNBC cell linesBreast cancerMiR-221/222Β-cateninHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Progression of TNBCGrowth factor receptor 2Limited treatment optionsWnt/β-catenin activationNegative breast cancerFactor receptor 2Primary tumor samplesWnt/β-catenin signalingCell linesWnt3a treatmentMultiple negative regulatorsΒ-catenin activationΒ-catenin signalingPatient survivalPoor prognosisTreatment options
2016
Activation of endothelial β-catenin signaling induces heart failure
Nakagawa A, Naito AT, Sumida T, Nomura S, Shibamoto M, Higo T, Okada K, Sakai T, Hashimoto A, Kuramoto Y, Oka T, Lee JK, Harada M, Ueda K, Shiojima I, Limbourg FP, Adams RH, Noda T, Sakata Y, Akazawa H, Komuro I. Activation of endothelial β-catenin signaling induces heart failure. Scientific Reports 2016, 6: 25009. PMID: 27146149, PMCID: PMC4857119, DOI: 10.1038/srep25009.Peer-Reviewed Original ResearchConceptsWnt/β-cateninHeart failureCardiac dysfunctionCa miceEndothelial cellsΒ-cateninEndothelial β-cateninProgressive cardiac dysfunctionCardiac endothelial cellsDegeneration of mitochondriaArterial endothelial cellsNeuregulin-ErbB signalingNeuregulin proteinΒ-catenin-dependent canonical WntEndothelial expressionIschemic diseasesTherapeutic targetDysfunctionMiceSustained activationFunction mutationsNeuregulin-ErbBT-tubulesCanonical WntConditional gain
2015
Second‐generation antisense oligonucleotides against β‐catenin protect mice against diet‐induced hepatic steatosis and hepatic and peripheral insulin resistance
Popov VB, Jornayvaz FR, Akgul EO, Kanda S, Jurczak MJ, Zhang D, Abudukadier A, Majumdar SK, Guigni B, Petersen KF, Manchem VP, Bhanot S, Shulman GI, Samuel VT. Second‐generation antisense oligonucleotides against β‐catenin protect mice against diet‐induced hepatic steatosis and hepatic and peripheral insulin resistance. The FASEB Journal 2015, 30: 1207-1217. PMID: 26644352, PMCID: PMC4750414, DOI: 10.1096/fj.15-271999.Peer-Reviewed Original ResearchConceptsHepatic steatosisInsulin resistanceAntisense oligonucleotideDiet-induced hepatic steatosisWhole-body glucose metabolismLipid-induced insulin resistanceMale C57BL/6 micePeripheral insulin resistanceHyperinsulinemic-euglycemic clampType 2 diabetesHepatic insulin sensitivityΒ-cateninHepatic lipid compositionWhite adipose tissueWnt/β-cateninΒ-catenin expressionMetabolic syndromeProtect miceC57BL/6 miceΒ-catenin mRNAFed miceHepatic triglyceridesInsulin sensitivityAwake miceGlucose metabolismPigment Epithelium-Derived Factor (PEDF) Inhibits Wnt/β-catenin Signaling in the Liver
Protiva P, Gong J, Sreekumar B, Torres R, Zhang X, Belinsky GS, Cornwell M, Crawford SE, Iwakiri Y, Chung C. Pigment Epithelium-Derived Factor (PEDF) Inhibits Wnt/β-catenin Signaling in the Liver. Cellular And Molecular Gastroenterology And Hepatology 2015, 1: 535-549.e14. PMID: 26473164, PMCID: PMC4604042, DOI: 10.1016/j.jcmgh.2015.06.006.Peer-Reviewed Original ResearchLow-density lipoprotein receptor-related protein 6Catenin signalingWnt coreceptor low-density lipoprotein receptor-related protein 6KO liversLipoprotein receptor-related protein 6Western diet feedingEpithelium-derived factorWnt/β-cateninHuman HCC cellsHuman HCC specimensInhibits Wnt/β-cateninMultiple tumor typesPEDF knockoutCarcinoma cell linesDiet feedingKO miceWestern dietHepatocellular carcinoma cell linesHCC formationHuman hepatocellular carcinoma cell lineTumor-suppressive propertiesPigment epitheliumTumor typesWnt5a proteinControl liversALDH1B1 Is Crucial for Colon Tumorigenesis by Modulating Wnt/β-Catenin, Notch and PI3K/Akt Signaling Pathways
Singh S, Arcaroli J, Chen Y, Thompson DC, Messersmith W, Jimeno A, Vasiliou V. ALDH1B1 Is Crucial for Colon Tumorigenesis by Modulating Wnt/β-Catenin, Notch and PI3K/Akt Signaling Pathways. PLOS ONE 2015, 10: e0121648. PMID: 25950950, PMCID: PMC4423958, DOI: 10.1371/journal.pone.0121648.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAldehyde Dehydrogenase, MitochondrialAnimalsCell Line, TumorColonic NeoplasmsGene Expression Regulation, NeoplasticHCT116 CellsHT29 CellsHumansMiceNeoplasm TransplantationPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, NotchRNA, Small InterferingSignal TransductionSpheroids, CellularWnt Signaling PathwayConceptsWnt/β-cateninPI3K/AktΒ-cateninSW-480 cellsColon cancer tumorigenesisWnt reporter activityPattern of expressionPI3K/Akt Signaling PathwayDual-luciferase reporterPI3K/Akt signal pathwayAkt Signaling PathwayTranscription factorsAkt signal pathwayNude mouse xenograft tumor modelColon tumorigenesisGene promoterColon adenocarcinoma cell lineMouse xenograft tumor modelALDH1B1 expressionAldehyde dehydrogenase 1B1Signaling pathwaysLuciferase reporterSize of spheroidsAdenocarcinoma cell lineXenograft tumor model
2014
Stem cells in gastrointestinal cancers: The road less travelled.
Mikhail S, Zeidan A. Stem cells in gastrointestinal cancers: The road less travelled. World Journal Of Stem Cells 2014, 6: 606-13. PMID: 25426257, PMCID: PMC4178260, DOI: 10.4252/wjsc.v6.i5.606.Peer-Reviewed Original ResearchCancer stem cellsGastrointestinal malignanciesNew therapeutic optionsFormation of CSCsGeneration of CSCsRole of dysregulationWnt/β-cateninStem cellsGastrointestinal neoplasmsTherapeutic optionsGastroesophageal tumorsGastrointestinal cancerTherapeutic strategiesTumor growthMalignant cellsMolecular abnormalitiesSignificant optimismCancerCancer resistanceΒ-cateninPatientsMalignancyTransformation growthPrecise targetingPotential utility
2013
Wnt3a mediated activation of Wnt/β-catenin signaling promotes tumor progression in glioblastoma
Kaur N, Chettiar S, Rathod S, Rath P, Muzumdar D, Shaikh M, Shiras A. Wnt3a mediated activation of Wnt/β-catenin signaling promotes tumor progression in glioblastoma. Molecular And Cellular Neuroscience 2013, 54: 44-57. PMID: 23337036, DOI: 10.1016/j.mcn.2013.01.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsCell Line, TumorCell MovementCell ProliferationCell Transformation, NeoplasticDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticGene SilencingGlioblastomaHumansMiceMice, Inbred NODMice, SCIDNeoplastic Stem CellsTranscription, GeneticWnt Signaling PathwayWnt1 ProteinWnt3A ProteinConceptsWnt/β-cateninDevelopmental signaling pathwaysTumor progressionΒ-cateninCancer stem cell hypothesisRole of Wnt3aStem cell hypothesisIntra-cranial tumoursStem-like cellsNovel therapeutic strategiesGlioma stemPromotes Tumor ProgressionSignaling pathwaysCell migrationDistinct populationsCell hypothesisGlioma tumorigenesisCell proliferationWnt3aTherapeutic strategiesMalignant transformationTumor developmentPathwayWntGlioma cells
2012
Parathyroid hormone-related protein activates Wnt signaling to specify the embryonic mammary mesenchyme
Hiremath M, Dann P, Fischer J, Butterworth D, Boras-Granic K, Hens J, Van Houten J, Shi W, Wysolmerski J. Parathyroid hormone-related protein activates Wnt signaling to specify the embryonic mammary mesenchyme. Development 2012, 139: 4239-4249. PMID: 23034629, PMCID: PMC3478689, DOI: 10.1242/dev.080671.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsbeta CateninCell DifferentiationFemaleGene Expression Regulation, DevelopmentalKeratinocytesLymphoid Enhancer-Binding Factor 1Mammary Glands, AnimalMesodermMiceMice, KnockoutParathyroid Hormone-Related ProteinReceptors, Parathyroid HormoneThrombospondinsWnt ProteinsWnt Signaling PathwayConceptsLoss of PTHrPOverexpression of PTHrPHormone-related proteinMammary mesenchymeΒ-cateninEmbryonic mammary mesenchymeWnt pathwayWnt/β-cateninEmbryonic mammary developmentCanonical Wnt pathwayPTHrPMammary developmentMammary budAbnormal differentiationReduced expressionBasal keratinocytesVentral skinReporter activityBud cellsMarkersCanonical WntInappropriate differentiationAbolished expressionMesenchyme markersOverexpressionWnt/β‐catenin signaling is hyperactivated in systemic sclerosis and induces Smad‐dependent fibrotic responses in mesenchymal cells
Wei J, Fang F, Lam AP, Sargent JL, Hamburg E, Hinchcliff ME, Gottardi CJ, Atit R, Whitfield ML, Varga J. Wnt/β‐catenin signaling is hyperactivated in systemic sclerosis and induces Smad‐dependent fibrotic responses in mesenchymal cells. Arthritis & Rheumatism 2012, 64: 2734-2745. PMID: 22328118, PMCID: PMC3553791, DOI: 10.1002/art.34424.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultbeta CateninBiopsyCase-Control StudiesCell MovementCell ProliferationCells, CulturedFibroblastsFibrosisFrizzled ReceptorsHumansIntercellular Signaling Peptides and ProteinsLymphoid Enhancer-Binding Factor 1MesodermRepressor ProteinsScleroderma, SystemicSignal TransductionSkinSmad ProteinsWnt ProteinsWnt3A ProteinConceptsWnt/β-cateninCanonical WntWnt-3aMesenchymal cellsGenome-wide expression dataAberrant Wnt/β-catenin pathway activationCell fate specificationΒ-cateninSkin biopsy specimensMyofibroblast differentiationCanonical Wnt/β-cateninWnt/β-catenin signalingWnt receptor Fzd2Subcutaneous preadipocytesSystemic sclerosisΒ-catenin signalingFate specificationBiopsy specimensΒ-catenin activationExpression of WntHuman mesenchymal cellsGrowth factor βPathway componentsGene expressionProfibrotic responsesEpithelial Wnt Ligand Secretion Is Required for Adult Hair Follicle Growth and Regeneration
Myung PS, Takeo M, Ito M, Atit RP. Epithelial Wnt Ligand Secretion Is Required for Adult Hair Follicle Growth and Regeneration. Journal Of Investigative Dermatology 2012, 133: 31-41. PMID: 22810306, PMCID: PMC3479363, DOI: 10.1038/jid.2012.230.Peer-Reviewed Original ResearchConceptsWnt ligand secretionHair follicle epitheliumFollicle growthHair follicle growthWnt ligandsEpithelial Wnt ligandsHair cycle arrestFollicular epitheliumLigand secretionFollicle epitheliumWnt/β-catenin activationΒ-cateninAnagen inductionWnt/β-cateninStem cell markersΒ-catenin activationPotential cellular targetsHair follicle stem cellsCellular sourceCell markersHair disordersFollicle stem cellsHair folliclesEpitheliumHair follicle regeneration
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