2024
Preclinical evaluation of avutometinib and defactinib in high‐grade endometrioid endometrial cancer
Hartwich T, Mansolf M, Demirkiran C, Greenman M, Bellone S, McNamara B, Nandi S, Alexandrov L, Yang‐Hartwich Y, Coma S, Pachter J, Santin A. Preclinical evaluation of avutometinib and defactinib in high‐grade endometrioid endometrial cancer. Cancer Medicine 2024, 13: e70210. PMID: 39240189, PMCID: PMC11378359, DOI: 10.1002/cam4.70210.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBenzamidesCarcinoma, EndometrioidCell Line, TumorCell ProliferationEndometrial NeoplasmsExome SequencingFemaleFocal Adhesion Kinase 1HumansImidazolesMiceNeoplasm GradingOxazepinesProtein Kinase InhibitorsPyrazinesSulfonamidesXenograft Model Antitumor AssaysConceptsFocal adhesion kinaseWhole-exome sequencingEndometrial cancer cell linesVS-4718Cell linesRas/MAPK pathwayPhosphorylated focal adhesion kinaseWestern blot assayWhole-exome sequencing resultsRAF/MEK inhibitionEAC cell linesBlot assayP-FAKGenetic landscapeCell cycleEndometrial cancerGenetic derangementsDefactinibP-MEKGrowth inhibitionRAF/MEKRas/MAPKCell viabilityP-ERKHigh-grade endometrial cancerIntegrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix
Bellone S, Jeong K, Halle M, Krakstad C, McNamara B, Greenman M, Mutlu L, Demirkiran C, Hartwich T, Yang-Hartwich Y, Zipponi M, Buza N, Hui P, Raspagliesi F, Lopez S, Paolini B, Milione M, Perrone E, Scambia G, Altwerger G, Ravaggi A, Bignotti E, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Quick C, Angioli R, Terranova C, Zaidi S, Nandi S, Alexandrov L, Siegel E, Choi J, Schlessinger J, Santin A. Integrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2321898121. PMID: 38625939, PMCID: PMC11046577, DOI: 10.1073/pnas.2321898121.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingPatient-derived-xenograftsBase excision repairCopy number lossMultiregion whole-exome sequencingCopy number gainHigh-grade neuroendocrine carcinomaCNV analysisPhylogenetic analysisEvolutionary historyNeuroendocrine cervical cancerHuman papillomavirus DNAMutator phenotypeSensitivity to afatinibGenetic landscapeRecurrent mutationsRNA sequencingGene fusionsMutational landscape analysisExcision repairGenesMutationsPan-HERConsistent with deficiencyNeuroendocrine carcinoma
2023
In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma.
Mutlu L, Manavella D, Bellone S, McNamara B, Harold J, Mauricio D, Siegel E, Buza N, Hui P, Hartwich T, Yang-Hartwich Y, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma. Molecular Cancer Therapeutics 2023, 22: 1404-1412. PMID: 37676984, DOI: 10.1158/1535-7163.mct-23-0126.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaAntibody-dependent cellular cytotoxicityT-DXdUSC patientsUSC cell linesTrastuzumab deruxtecanSerous carcinomaHER2 expressionClinical trialsRecurrent uterine serous carcinomaTopoisomerase I inhibitor payloadSignificant antibody-dependent cellular cytotoxicityCell linesMultiple tumor indicationsPrimary USC cell linesLow HER2 expressionFuture clinical trialsHigh recurrence ratePeripheral blood lymphocytesERBB2 gene amplificationGrowth suppressionHER2-overexpressing cell linesTumor growth suppressionOverall survivalStandard chemotherapyMonitoring Treatment Response, Early Recurrence, and Survival in Uterine Serous Carcinoma and Carcinosarcoma Patients Using Personalized Circulating Tumor DNA Biomarkers
Bellone S, McNamara B, Mutlu L, Demirkiran C, Hartwich T, Harold J, Yang-Hartwich Y, Siegel E, Santin A. Monitoring Treatment Response, Early Recurrence, and Survival in Uterine Serous Carcinoma and Carcinosarcoma Patients Using Personalized Circulating Tumor DNA Biomarkers. International Journal Of Molecular Sciences 2023, 24: 8873. PMID: 37240216, PMCID: PMC10219151, DOI: 10.3390/ijms24108873.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaCS patientsEarly recurrenceDroplet digital polymerase chain reactionCA 125Serous carcinomaCtDNA testingTime of surgeryTime of recurrenceReliable tumor biomarkersTumour DNA biomarkersCarcinosarcoma patientsUSC patientsRecurrent diseaseOccult diseaseOverall survivalEndometrial cancerAggressive variantInitial treatmentRecurrent tumorsResidual tumorClinical findingsTreatment courseTreatment trialsPIK3CA mutationsUterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor
McNamara B, Harold J, Manavella D, Bellone S, Mutlu L, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Yang K, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Burton E, Inagaki H, Albers A, Zhang C, Bollag G, Schlessinger J, Santin A. Uterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor. Gynecologic Oncology 2023, 172: 65-71. PMID: 36958197, PMCID: PMC10192120, DOI: 10.1016/j.ygyno.2023.03.009.Peer-Reviewed Original ResearchConceptsUterine leiomyosarcomaPDX modelsGain of functionMedian overall survivalPhase I trialOral gavage dailyVivo activityTumor growth inhibitionTumor volume differencesTumor cell proliferationOverall survivalTolerable toxicityI trialOral treatmentTreatment cohortsGavage dailyAggressive tumorsSCID miceULMS patientsPK studiesTumor samplesWestern blotCell proliferationControl vehicleLeiomyosarcomaNRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8
Anandhan A, Dodson M, Shakya A, Chen J, Liu P, Wei Y, Tan H, Wang Q, Jiang Z, Yang K, Garcia J, Chambers S, Chapman E, Ooi A, Yang-Hartwich Y, Stockwell B, Zhang D. NRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8. Science Advances 2023, 9: eade9585. PMID: 36724221, PMCID: PMC9891695, DOI: 10.1126/sciadv.ade9585.Peer-Reviewed Original ResearchConceptsLabile iron poolNFE2L2/Human ovarian cancer tissuesCancer cellsOvarian cancer cell linesOvarian cancer tissuesIntracellular labile iron poolIron homeostasisCancer cell linesPreclinical modelsNrf2 inhibitionCancer tissuesNrf2 levelsCancer treatmentFerroptotic deathNrf2Ferroptosis resistanceKnockout cellsCell linesUntapped strategyFerroptosisIron poolCellsHomeostasisExpressionThe Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo
Han C, McNamara B, Bellone S, Harold J, Manara P, Hartwich T, Mutlu L, Yang-Hartwich Y, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. The Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo. Gynecologic Oncology 2023, 170: 172-178. PMID: 36706643, PMCID: PMC10023457, DOI: 10.1016/j.ygyno.2023.01.015.Peer-Reviewed Original ResearchConceptsCombination of olaparibOvarian cancerHER2 expressionSingle agentCell linesGynecologic cancer mortalityHER2-negative tumorsOvarian cancer cell linesOvarian cancer patientsEpithelial ovarian carcinomaNovel therapeutic optionsOC cell linesUnmet medical needPoly (ADP-ribose) polymerase (PARP) inhibitorsPan-ErbB inhibitorSingle-agent olaparibPolymerase inhibitor olaparibPoly (ADP-ribose) polymerase (PARP) inhibitor olaparibPrimary HER2Cancer cell linesNegative tumorsTherapeutic optionsCancer mortalityCancer patientsNeu expressionTrastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression
Mauricio D, Bellone S, Mutlu L, McNamara B, Manavella D, Demirkiran C, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression. Gynecologic Oncology 2023, 170: 38-45. PMID: 36610380, PMCID: PMC10445234, DOI: 10.1016/j.ygyno.2022.12.018.Peer-Reviewed Original ResearchConceptsHER2/neu expressionDS-8201aAntibody-drug conjugatesNeu expressionCS cell linesTrastuzumab deruxtecanOvarian carcinosarcomaTopoisomerase I inhibitor payloadCell linesAggressive gynecologic malignancyLimited therapeutic optionsEffective antibody-drug conjugatesCarcinosarcoma cell lineGynecologic malignanciesTherapeutic optionsIsotype controlSarcomatous elementsXenograft modelBystander killingFlow cytometryTumor cellsCarcinosarcomaAntitumor activityVivo studiesVivo activity
2022
Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor
Manavella D, McNamara B, Harold J, Bellone S, Hartwich T, Yang-Hartwich Y, Mutlu L, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Dottino P, Choi J, Alexandrov L, Buza N, Hui P, Santin A. Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor. Gynecologic Oncology 2022, 169: 98-105. PMID: 36525930, PMCID: PMC9925406, DOI: 10.1016/j.ygyno.2022.12.003.Peer-Reviewed Original ResearchConceptsHomologous recombination deficiencyCS cell linesCell linesWestern blotKinase inhibitorsOverall animal survivalProtein expressionDose-dependent increaseDose-dependent inhibitionCarcinosarcoma cell lineTumor growth inhibitionCaspase-3 expressionEndometrioid histologyAggressive malignancyUterine carcinosarcomaCS patientsPreclinical activityClinical trialsEpithelial componentAnimal survivalXenograftsApoptosis markersRecombination deficiencyP-ATRP-Chk1Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma
Harold J, Bellone S, Manavella D, Mutlu L, McNamara B, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Santin A. Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma. Gynecologic Oncology 2022, 168: 157-165. PMID: 36442427, PMCID: PMC9797429, DOI: 10.1016/j.ygyno.2022.11.014.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsUterine leiomyosarcomaVivo activityVehicle control treatmentMedian overall survivalTumor volume differencesOral scheduleWestern blot analysisOverall survivalOral gavageAggressive malignancyPDX modelsClinical trialsSCID miceTumor measurementsULMS patientsSignificant growth inhibitionNovel ATR inhibitorTumor samplesSignificant toxicityWestern blotKinase inhibitorsATRX mutationsGene mutationsControl vehicleHomologous recombination deficiency (HRD) signature-3 in ovarian and uterine carcinosarcomas correlates with preclinical sensitivity to Olaparib, a poly (adenosine diphosphate [ADP]- ribose) polymerase (PARP) inhibitor
Tymon-Rosario JR, Manara P, Manavella DD, Bellone S, Hartwich TMP, Harold J, Yang-Hartwich Y, Zipponi M, Choi J, Jeong K, Mutlu L, Yang K, Altwerger G, Menderes G, Ratner E, Huang GS, Clark M, Andikyan V, Azodi M, Schwartz PE, Alexandrov LB, Santin AD. Homologous recombination deficiency (HRD) signature-3 in ovarian and uterine carcinosarcomas correlates with preclinical sensitivity to Olaparib, a poly (adenosine diphosphate [ADP]- ribose) polymerase (PARP) inhibitor. Gynecologic Oncology 2022, 166: 117-125. PMID: 35599167, DOI: 10.1016/j.ygyno.2022.05.005.Peer-Reviewed Original ResearchConceptsUterine carcinosarcomaCS cell linesSignature 3Cell linesPolymerase inhibitorsOverall animal survivalFresh tumor samplesPoly (ADP-ribose) polymerase (PARP) inhibitorsXenograft tumor growthG2/M phaseAggressive malignancyCS patientsPrimary tumorCell cycle arrestPrimary cell linesPoor survivalClinical studiesPreclinical sensitivityCarcinosarcomaTumor growthAnimal survivalOlaparib activityTumor samplesOlaparibAntitumor activity
2021
A 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 cavityProgression of Cystadenoma to Mucinous Borderline Ovarian Tumor in Young Females: Case Series and Literature Review
Beroukhim G, Ozgediz D, Cohen PJ, Hui P, Morotti R, Schwartz PE, Yang-Hartwich, Vash-Margita A. Progression of Cystadenoma to Mucinous Borderline Ovarian Tumor in Young Females: Case Series and Literature Review. Journal Of Pediatric And Adolescent Gynecology 2021, 35: 359-367. PMID: 34843973, DOI: 10.1016/j.jpag.2021.11.003.Peer-Reviewed Original ResearchConceptsMucinous borderline ovarian tumorsBorderline ovarian tumorsOvarian tumorsYale-New Haven HospitalRetrospective chart reviewBenign ovarian tumorsBenign ovarian lesionsRate of recurrenceNew Haven HospitalAbdominal painPreoperative characteristicsChart reviewDisease recurrenceRecurrent cystsCase seriesChief complaintClinical presentationClinicopathologic featuresFemale patientsMucinous cystadenomaOvarian cystsOvarian lesionsTumor stageAdolescent patientsSubsequent surveillancePersonalized models of heterogeneous 3D epithelial tumor microenvironments: Ovarian cancer as a model
Horst EN, Bregenzer ME, Mehta P, Snyder CS, Repetto T, Yang-Hartwich Y, Mehta G. Personalized models of heterogeneous 3D epithelial tumor microenvironments: Ovarian cancer as a model. Acta Biomaterialia 2021, 132: 401-420. PMID: 33940195, PMCID: PMC8969826, DOI: 10.1016/j.actbio.2021.04.041.Peer-Reviewed Original ResearchConceptsOptimal adjuvant treatmentTumor microenvironmentOvarian cancerCancer modelAdverse clinical outcomesHeterogeneous patient populationMinimal residual diseaseDifferent tumor locationsConventional cancer treatmentsEpithelial tumor microenvironmentModels of cancerAdjuvant treatmentDurable responsesTreatment failureClinical outcomesResidual diseasePatient populationTumor locationDisease progressionEffective therapyFundamental cancer biologyDiverse tumor microenvironmentsIndividual patientsSame patientPatient biopsies
2020
Identification of miPEP133 as a novel tumor-suppressor microprotein encoded by miR-34a pri-miRNA
Kang M, Tang B, Li J, Zhou Z, Liu K, Wang R, Jiang Z, Bi F, Patrick D, Kim D, Mitra AK, Yang-Hartwich Y. Identification of miPEP133 as a novel tumor-suppressor microprotein encoded by miR-34a pri-miRNA. Molecular Cancer 2020, 19: 143. PMID: 32928232, PMCID: PMC7489042, DOI: 10.1186/s12943-020-01248-9.Peer-Reviewed Original ResearchConceptsNon-coding RNA transcriptsNasopharyngeal carcinomaCancer cell linesP53 transcriptional activationPrognostic markerTumor suppressor functionAmino acid residuesCell linesTumor growthNovel microproteinWild-type p53Cellular functionsMetastatic nasopharyngeal carcinomaTranscriptional activationPotential prognostic markerMitochondrial membraneUnfavorable prognostic markerCervical cancer cell linesRNA transcriptsMitochondrial massTumor suppressorMiR-34a expressionAcid residuesNormal human colonNPC clinical samplesIn vivo modeling of metastatic human high-grade serous ovarian cancer in mice
Kim O, Park EY, Klinkebiel DL, Pack SD, Shin YH, Abdullaev Z, Emerson RE, Coffey DM, Kwon SY, Creighton CJ, Kwon S, Chang EC, Chiang T, Yatsenko AN, Chien J, Cheon DJ, Yang-Hartwich Y, Nakshatri H, Nephew KP, Behringer RR, Fernández FM, Cho CH, Vanderhyden B, Drapkin R, Bast RC, Miller KD, Karpf AR, Kim J. In vivo modeling of metastatic human high-grade serous ovarian cancer in mice. PLOS Genetics 2020, 16: e1008808. PMID: 32497036, PMCID: PMC7297383, DOI: 10.1371/journal.pgen.1008808.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorChromosomal InstabilityCystadenocarcinoma, SerousDEAD-box RNA HelicasesDisease Models, AnimalDNA RepairDrug Resistance, NeoplasmDrug Screening Assays, AntitumorFeasibility StudiesFemaleHumansMiceMice, KnockoutMutationNeoplasm GradingNeoplasm MetastasisOvarian NeoplasmsPeritoneal NeoplasmsPrimary Cell CulturePTEN PhosphohydrolaseRibonuclease IIITumor Suppressor Protein p53ConceptsHigh-grade serous carcinomaHuman HGSCHigh-grade serous ovarian cancerSerous ovarian cancerOvarian cancerPeritoneal metastasisHuman high-grade serous ovarian cancerMetastatic ovarian cancerOvarian cancer typesHuman cancer metastasisHuman cancer mortalityHemorrhagic ascitesClinical metastasisHistopathological similaritiesSerous carcinomaCancer mortalityFallopian tubeMurine modelPeritoneal cavityMouse modelPotential therapyMouse deathMetastasisCancer typesCancer metastasis
2019
An Underlying Mechanism of Dual Wnt Inhibition and AMPK Activation: Mitochondrial Uncouplers Masquerading as Wnt Inhibitors
Zhang W, Sviripa VM, Kril L, Yu T, Xie Y, Hubbard W, Sullivan P, Chen X, Zhan CG, Yang-Hartwich Y, Evers BM, Spear B, Gedaly R, Watt DS, Liu C. An Underlying Mechanism of Dual Wnt Inhibition and AMPK Activation: Mitochondrial Uncouplers Masquerading as Wnt Inhibitors. Journal Of Medicinal Chemistry 2019, 62: 11348-11358. PMID: 31774672, PMCID: PMC7560992, DOI: 10.1021/acs.jmedchem.9b01685.Peer-Reviewed Original ResearchTumor microenvironment and immunology of ovarian cancer: 12th Biennial Rivkin Center Ovarian Cancer Research Symposium
Mitra AK, Yang-Hartwich Y. Tumor microenvironment and immunology of ovarian cancer: 12th Biennial Rivkin Center Ovarian Cancer Research Symposium. International Journal Of Gynecological Cancer 2019, 29: s12. PMID: 31462543, DOI: 10.1136/ijgc-2019-000666.Peer-Reviewed Original ResearchInhibition 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