2019
Inhibition of Heat Shock Protein 90 suppresses TWIST1 Transcription
Chong KY, Kang M, Garofalo F, Ueno D, Liang H, Cady S, Madarikan O, Pitruzzello N, Tsai CH, Hartwich T, Shuch B, Yang-Hartwich Y. Inhibition of Heat Shock Protein 90 suppresses TWIST1 Transcription. Molecular Pharmacology 2019, 96: 168-179. PMID: 31175180, DOI: 10.1124/mol.119.116137.Peer-Reviewed Original ResearchMeSH KeywordsBenzoquinonesCell Line, TumorDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHSP90 Heat-Shock ProteinsHumansKidney NeoplasmsLactams, MacrocyclicNasopharyngeal NeoplasmsNuclear ProteinsOvarian NeoplasmsPhosphorylationPromoter Regions, GeneticSTAT3 Transcription FactorTissue Array AnalysisTranscription, GeneticTwist-Related Protein 1ConceptsEpithelial-mesenchymal transitionHsp90 inhibitorsTwist1 transcriptionMolecular chaperone heat shock protein 90Chaperone heat shock protein 90Involvement of Hsp90Heat shock protein 90Cancer cell linesRole of Hsp90Binding of STAT3Inhibition of Hsp90Shock protein 90Cell linesProximity ligation assayHsp90 inhibitor 17TWIST1 mRNA expressionTranscription factorsSignal transducerProtein 90Promoter activityTranscription 3New therapeutic opportunitiesHsp90Molecular mechanismsSTAT3 activityProtein kinase Cα–mediated phosphorylation of Twist1 at Ser-144 prevents Twist1 ubiquitination and stabilizes it
Tedja R, Roberts CM, Alvero AB, Cardenas C, Yang-Hartwich Y, Spadinger S, Pitruzzello M, Yin G, Glackin CA, Mor G. Protein kinase Cα–mediated phosphorylation of Twist1 at Ser-144 prevents Twist1 ubiquitination and stabilizes it. Journal Of Biological Chemistry 2019, 294: 5082-5093. PMID: 30733340, PMCID: PMC6442047, DOI: 10.1074/jbc.ra118.005921.Peer-Reviewed Original ResearchConceptsProtein kinase CPhosphorylation sitesHelix transcription factorPhosphorylation of Twist1Candidate phosphorylation sitesProtein kinase CαCombination of immunoblottingUbiquitination eventsTwist1 phosphorylationTranscription factorsEmbryonic developmentKnockout experimentsSer-144CRISPR/Twist1 proteinKinase CInvasive phenotypeAdult cellsPhosphorylationTwist1UbiquitinationCancer developmentCell linesTwist1 expressionPKCα
2016
TRX-E-002-1 Induces c-Jun–Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo
Alvero AB, Heaton A, Lima E, Pitruzzello M, Sumi N, Yang-Hartwich Y, Cardenas C, Steinmacher S, Silasi DA, Brown D, Mor G. TRX-E-002-1 Induces c-Jun–Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo. Molecular Cancer Therapeutics 2016, 15: 1279-1290. PMID: 27196760, DOI: 10.1158/1535-7163.mct-16-0005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Line, TumorCell ProliferationCell SurvivalCisplatinDrug Resistance, NeoplasmDrug SynergismFemaleFlavonoidsGene Expression Regulation, NeoplasticHumansMiceNeoplasm Recurrence, LocalNeoplasm TransplantationNeoplastic Stem CellsOvarian NeoplasmsPhosphorylationProto-Oncogene Proteins c-junSignal TransductionXenograft Model Antitumor AssaysConceptsCancer stem cellsOvarian cancer cellsTumor burdenOvarian cancerCancer cellsChemoresistant cancer stem cellsOvarian cancer stem cellsIntraperitoneal tumor burdenRecurrent ovarian cancerBest therapeutic optionManagement of patientsCombination of cisplatinEpithelial ovarian cancerCell deathStem cellsTumor repairDisease recurrenceMaintenance treatmentPatient survivalTherapeutic optionsHigh mortalityStemness propertiesMonotherapyDeathVehicle control