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
p53-Pirh2 Complex Promotes Twist1 Degradation and Inhibits EMT
Yang-Hartwich Y, Tedja R, Roberts C, Goodner-Bingham J, Cardenas C, Gurea M, Sumi NJ, Alvero AB, Glackin CA, Mor G. p53-Pirh2 Complex Promotes Twist1 Degradation and Inhibits EMT. Molecular Cancer Research 2019, 17: molcanres.0238.2018. PMID: 30131448, PMCID: PMC6800184, DOI: 10.1158/1541-7786.mcr-18-0238.Peer-Reviewed Original ResearchConceptsEpithelial-mesenchymal transitionTwist1 degradationInvasive cancer phenotypeEMT-inducing transcription factorsAbility of p53Tumor suppressor geneTumor cell invasivenessWild-type p53Proteasomal degradationTranscription factorsTwist1 proteinSuppressor geneEpithelial phenotypeInhibits epithelial-mesenchymal transitionCancer phenotypeMolecular levelCell invasivenessCancer progressionCancer metastasisWt p53Twist1P53Metastatic processTumor progressionNew insights
2018
Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors
Li C, Bonazzoli E, Bellone S, Choi J, Dong W, Menderes G, Altwerger G, Han C, Manzano A, Bianchi A, Pettinella F, Manara P, Lopez S, Yadav G, Riccio F, Zammataro L, Zeybek B, Yang-Hartwich Y, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Zizioli V, Odicino F, Pecorelli S, Ardighieri L, Silasi DA, Litkouhi B, Ratner E, Azodi M, Huang GS, Schwartz PE, Lifton RP, Schlessinger J, Santin AD. Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 116: 619-624. PMID: 30584090, PMCID: PMC6329978, DOI: 10.1073/pnas.1814027116.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAzepinesBRCA1 ProteinBRCA2 ProteinCell Line, TumorClass I Phosphatidylinositol 3-KinasesFemaleHumansMiceMutationNeoplasm MetastasisNeoplasm Recurrence, LocalOvarian NeoplasmsProteinsProto-Oncogene Proteins c-mycTriazolesTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsOvarian cancerWhole-exome sequencingC-myc amplificationRecurrent tumorsPrimary tumorBET inhibitorsChemotherapy-resistant diseaseRecurrent ovarian cancerLethal gynecologic malignancyBilateral ovarian cancerChemotherapy-resistant tumorsPrimary metastatic tumorsMutational landscapeSomatic mutationsFresh-frozen tumorsGynecologic malignanciesMetastatic tumorsPrimary cell linesC-MYC gainPIK3CA amplificationTranscoelomic metastasisTherapeutic targetPatientsMetastatic abilityTumors
2014
p53 protein aggregation promotes platinum resistance in ovarian cancer
Yang-Hartwich Y, Soteras MG, Lin ZP, Holmberg J, Sumi N, Craveiro V, Liang M, Romanoff E, Bingham J, Garofalo F, Alvero A, Mor G. p53 protein aggregation promotes platinum resistance in ovarian cancer. Oncogene 2014, 34: 3605-3616. PMID: 25263447, DOI: 10.1038/onc.2014.296.Peer-Reviewed Original ResearchConceptsPro-apoptotic functionP53 aggregationProtein aggregationP53 aggregatesNormal transcriptional activationTwo-dimensional gel electrophoresisCancer cellsCancer cell survivalKey transcriptional factorGenetic mutationsHigh-grade serous ovarian carcinomaP53 inactivationP53 proteinStem cell propertiesCancer stem cell propertiesCellular homeostasisTranscriptional activationCancer stem cellsTranscriptional factorsTumor-initiating capacityP53 turnoverCell survivalHGSOC cellsStem cellsPotential therapeutic targetDetection of p53 Protein Transcriptional Activity by Chromatin Immunoprecipitation
Yang-Hartwich Y, Romanoff E, Bingham J, Alvero AB, Mor G. Detection of p53 Protein Transcriptional Activity by Chromatin Immunoprecipitation. Methods In Molecular Biology 2014, 1219: 87-93. PMID: 25308264, DOI: 10.1007/978-1-4939-1661-0_8.Peer-Reviewed Original ResearchMeSH KeywordsChromatin ImmunoprecipitationGene Expression Regulation, NeoplasticHumansNeoplasmsReal-Time Polymerase Chain ReactionTranscription, GeneticTumor Suppressor Protein p53ConceptsTranscriptional activityP53 transcriptional activityChromatin immunoprecipitationTranscription-dependent activityDNA-binding domainExpression of hundredsImportant cellular functionsKey transcriptional mediatorAbility of p53Protein's transcriptional activityP53-induced apoptosisResult of mutationsGenome integrityCellular homeostasisCellular functionsTranscriptional mediatorsTarget genesPromoter regionApoptotic genesCell deathReal-time quantitative polymerase chain reactionCancer cellsQuantitative polymerase chain reactionImmunoprecipitationGenesDetection of p53 Protein Aggregation in Cancer Cell Lines and Tumor Samples
Yang-Hartwich Y, Bingham J, Garofalo F, Alvero AB, Mor G. Detection of p53 Protein Aggregation in Cancer Cell Lines and Tumor Samples. Methods In Molecular Biology 2014, 1219: 75-86. PMID: 25308263, DOI: 10.1007/978-1-4939-1661-0_7.Peer-Reviewed Original ResearchMeSH KeywordsAmyloidApoptosisCell Line, TumorFluorescent Antibody TechniqueHumansImmunoblottingNeoplasmsTumor Suppressor Protein p53ConceptsCancer cell linesPro-apoptotic functionAggregation of p53P53 proteinCancer cellsCell linesP53 aggregationAmyloid-like oligomersProtein aggregationApoptotic signalsInactive conformationTumor samplesFunctional p53ProteinGenetic mutationsTumor progressionCentral roleP53Dysfunctional p53 proteinCellsAggregationMutationsApoptosisDeregulationLines