Featured Publications
ZNF397 Deficiency Triggers TET2-driven Lineage Plasticity and AR-Targeted Therapy Resistance in Prostate Cancer
Xu Y, Yang Y, Wang Z, Sjostrom M, Jiang Y, Tang Y, Cheng S, Deng S, Wang C, Gonzalez J, Johnson N, Li X, Li X, Metang L, Mukherji A, Xu Q, Tirado C, Wainwright G, Yu X, Barnes S, Hofstad M, Chen Y, Zhu H, Hanker A, Raj G, Zhu G, He H, Wang Z, Arteaga C, Liang H, Feng F, Wang Y, Wang T, Mu P. ZNF397 Deficiency Triggers TET2-driven Lineage Plasticity and AR-Targeted Therapy Resistance in Prostate Cancer. Cancer Discovery 2024, 14: 1496-1521. PMID: 38591846, PMCID: PMC11285331, DOI: 10.1158/2159-8290.cd-23-0539.Peer-Reviewed Original ResearchConceptsLineage plasticityTherapy resistanceProstate cancerCancer cellsAndrogen receptorResistance to AR-targeted therapiesLuminal lineageAR-targeted therapiesOvercome therapy resistanceTransition of cancer cellsEpigenetic regulatory machineryBona fide coactivatorTherapy responseAR signalingEpigenetic rewiringDrug resistanceTherapeutic strategiesEpigenetic reprogrammingProstateTherapyCancerPhenotypic plasticityRegulatory machineryAndrogenTranscriptional programsLoss of CHD1 Promotes Heterogeneous Mechanisms of Resistance to AR-Targeted Therapy via Chromatin Dysregulation
Zhang Z, Zhou C, Li X, Barnes S, Deng S, Hoover E, Chen C, Lee Y, Zhang Y, Wang C, Metang L, Wu C, Tirado C, Johnson N, Wongvipat J, Navrazhina K, Cao Z, Choi D, Huang C, Linton E, Chen X, Liang Y, Mason C, de Stanchina E, Abida W, Lujambio A, Li S, Lowe S, Mendell J, Malladi V, Sawyers C, Mu P. Loss of CHD1 Promotes Heterogeneous Mechanisms of Resistance to AR-Targeted Therapy via Chromatin Dysregulation. Cancer Cell 2020, 37: 584-598.e11. PMID: 32220301, PMCID: PMC7292228, DOI: 10.1016/j.ccell.2020.03.001.Peer-Reviewed Original ResearchMeSH KeywordsAndrogen AntagonistsAnimalsApoptosisBiomarkers, TumorCell ProliferationChromatinDNA HelicasesDNA-Binding ProteinsDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHigh-Throughput Screening AssaysHumansMaleMiceProstatic Neoplasms, Castration-ResistantReceptors, AndrogenRNA, Small InterferingTranscription FactorsTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsAntiandrogen resistanceChromatin dysregulationCHD1 lossProstate cancerGenomic copy number alterationsRNA-seq analysisResistance to hormonal therapyCopy number alterationsAR-targeted therapiesMetastatic prostate cancerATAC-seqClosed chromatinRNA-seqTranscriptional plasticityTranscription factorsFunctional screeningTranscriptomic changesMechanisms of resistanceHormone therapyLineage programsChromatinCHD1Global changeIntegrated analysisTherapyAn allelic series of miR-17∼92–mutant mice uncovers functional specialization and cooperation among members of a microRNA polycistron
Han Y, Vidigal J, Mu P, Yao E, Singh I, González A, Concepcion C, Bonetti C, Ogrodowski P, Carver B, Selleri L, Betel D, Leslie C, Ventura A. An allelic series of miR-17∼92–mutant mice uncovers functional specialization and cooperation among members of a microRNA polycistron. Nature Genetics 2015, 47: 766-775. PMID: 26029871, PMCID: PMC4485521, DOI: 10.1038/ng.3321.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisB-LymphocytesCarcinogenesisCells, CulturedEyelidsGene FrequencyGenes, LethalGenome-Wide Association StudyIntellectual DisabilityLimb Deformities, CongenitalMaleMice, 129 StrainMice, Inbred C57BLMice, TransgenicMicrocephalyMicroRNAsMultigene FamilyMutationTracheoesophageal Fistula
2024
Hyd/UBR5 defines a tumor suppressor pathway that links Polycomb repressive complex to regulated protein degradation in tissue growth control and tumorigenesis
Wen P, Lei H, Deng H, Deng S, Tirado C, Wang M, Mu P, Zheng Y, Pan D. Hyd/UBR5 defines a tumor suppressor pathway that links Polycomb repressive complex to regulated protein degradation in tissue growth control and tumorigenesis. Genes & Development 2024, 38: 675-691. PMID: 39137945, PMCID: PMC11368183, DOI: 10.1101/gad.351856.124.Peer-Reviewed Original ResearchConceptsPolycomb Repressive Complex1Tumor suppressor pathwayTissue growth controlSuppressor pathwayProtein degradationZinc finger genesGrowth controlUbiquitin-mediated degradationE3 ubiquitin ligasePolycomb repressive complexesProtein degradation pathwaysTumor suppressor geneHyperplastic discsFinger genesMammalian homologSubstrate adaptorRepressive complexesUbiquitin ligaseEmbryonic segmentationProtein complexesModel organismsHuman geneticsUpstream regulatorSuppressor geneProstate cancer tumorigenesis
2023
The Critical Interplay of CAF Plasticity and Resistance in Prostate Cancer.
Li X, Mu P. The Critical Interplay of CAF Plasticity and Resistance in Prostate Cancer. Cancer Research 2023, 83: 2990-2992. PMID: 37504898, DOI: 10.1158/0008-5472.can-23-2260.Commentaries, Editorials and LettersConceptsCastration-resistant prostate cancerAndrogen deprivation therapyProstate cancerAndrogen receptorCastration-resistant prostate cancer developmentDevelopment of castration-resistant prostate cancerGenetically engineered mouse modelsMyofibroblastic cancer-associated fibroblastsOvercome treatment resistanceCancer-associated fibroblastsIncreased tumor heterogeneityDeprivation therapyCRPC developmentProstate tumorsTumor microenvironmentLineage plasticityTreatment resistanceStromal compartmentStandard treatmentTumor heterogeneityCancer recurrenceDrug resistanceDisease progressionMouse modelSingle-cell RNA sequencing
2020
Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer
Zhang Z, Karthaus W, Lee Y, Gao V, Wu C, Russo J, Liu M, Mota J, Abida W, Linton E, Lee E, Barnes S, Chen H, Mao N, Wongvipat J, Choi D, Chen X, Zhao H, Manova-Todorova K, de Stanchina E, Taplin M, Balk S, Rathkopf D, Gopalan A, Carver B, Mu P, Jiang X, Watson P, Sawyers C. Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer. Cancer Cell 2020, 38: 279-296.e9. PMID: 32679108, PMCID: PMC7472556, DOI: 10.1016/j.ccell.2020.06.005.Peer-Reviewed Original ResearchMeSH KeywordsAndrogen AntagonistsAnimalsCancer-Associated FibroblastsCell Line, TumorCell ProliferationCells, CulturedDrug Resistance, NeoplasmGene Expression ProfilingGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMaleMice, SCIDNeuregulin-1Prostatic NeoplasmsTumor MicroenvironmentXenograft Model Antitumor AssaysConceptsCancer-associated fibroblastsProstate cancerAntiandrogen resistanceNeuregulin-1Second-generation antiandrogen therapyResistance to hormonal therapyCastration-resistant prostate cancerTreat advanced prostate cancerProstate organoid culturesSecond-generation antiandrogensAdvanced prostate cancerActivation of HER3Antiandrogen therapyHormone therapyHormone deprivationPharmacological blockadeTargeted therapyParacrine mechanismsTumor cellsMouse modelProstateClinical testingOrganoid culturesTherapyCancer
2019
The paracrine induction of prostate cancer progression by caveolin-1
Lin C, Yun E, Lo U, Tai Y, Deng S, Hernandez E, Dang A, Chen Y, Saha D, Mu P, Lin H, Li T, Shen T, Lai C, Hsieh J. The paracrine induction of prostate cancer progression by caveolin-1. Cell Death & Disease 2019, 10: 834. PMID: 31685812, PMCID: PMC6828728, DOI: 10.1038/s41419-019-2066-3.Peer-Reviewed Original ResearchConceptsCastration-resistant prostate cancerCancer stem cellsTumor-derived exosomesProstate cancerCav-1Cancer progressionSubpopulation of cancer stem cellsAssociated with stem cell phenotypeCancer immune evasionProstate cancer progressionStem cell capabilitiesStem cell phenotypePromote cancer developmentPresence of Cav-1Heterogeneous cancer cell populationsCancer cell populationsNeuroendocrine differentiationNeuroendocrine transdifferentiationEpithelial-mesenchymal transitionNFkB signaling pathwayTherapeutic resistanceTumor cellsImmune evasionChemotherapeutic resistanceParacrine induction
2017
Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance
Ku S, Rosario S, Wang Y, Mu P, Seshadri M, Goodrich Z, Goodrich M, Labbé D, Gomez E, Wang J, Long H, Xu B, Brown M, Loda M, Sawyers C, Ellis L, Goodrich D. Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. Science 2017, 355: 78-83. PMID: 28059767, PMCID: PMC5367887, DOI: 10.1126/science.aah4199.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAndrogen AntagonistsAnimalsCell Line, TumorCell LineageCell PlasticityDrug Resistance, NeoplasmEnhancer of Zeste Homolog 2 ProteinEpigenesis, GeneticHumansMaleMiceMutationNeoplasm MetastasisNeoplasms, ExperimentalNeuroendocrine TumorsProstatic NeoplasmsPTEN PhosphohydrolaseRetinoblastoma-Like Protein p107SOXB1 Transcription FactorsTumor Suppressor Protein p53ConceptsAntiandrogen therapyLineage plasticityClinical responses to antiandrogen therapyResistance to antiandrogen therapyMouse modelMetastasis of prostatic adenocarcinomaResponse to antiandrogen therapyAndrogen receptor expressionProstate cancer progressionLoss of Trp53Lineage marker expressionVariant histologyProstatic adenocarcinomaRB1 lossProstate cancerReceptor expressionPTEN mutationsAntiandrogen resistanceTherapeutic resistanceMouse tumorsGene expression profilesNeuroendocrine variantsReprogramming factorsProstateHuman tumors
2012
Intact p53-Dependent Responses in miR-34–Deficient Mice
Concepcion C, Han Y, Mu P, Bonetti C, Yao E, D'Andrea A, Vidigal J, Maughan W, Ogrodowski P, Ventura A. Intact p53-Dependent Responses in miR-34–Deficient Mice. PLOS Genetics 2012, 8: e1002797. PMID: 22844244, PMCID: PMC3406012, DOI: 10.1371/journal.pgen.1002797.Peer-Reviewed Original ResearchConceptsMiR-34 familyMiR-34 expressionP53 pathwayP53-induced cell cycle arrestP53-independent functionsP53-dependent responseCell cycle arrestMiR-34Potential tumor suppressorExpression of membersP53-deficient miceP53-independentFamily of miRNAsP53 functionCycle arrestTumor suppressorMicroRNA familyCellular proliferation in vitroHuman cancersProliferation in vitroP53Brains of miceMicroRNAsNormal developmentMice
2010
Widespread regulatory activity of vertebrate microRNA* species
Yang J, Phillips M, Betel D, Mu P, Ventura A, Siepel A, Chen K, Lai E. Widespread regulatory activity of vertebrate microRNA* species. RNA 2010, 17: 312-326. PMID: 21177881, PMCID: PMC3022280, DOI: 10.1261/rna.2537911.Peer-Reviewed Original ResearchConceptsAnalysis of microarray dataVertebrate regulatory networksStudy of miRNA functionMiRNA:miRNARelevant to oncogenesisFraction of miRNAsTranscriptome-wide evidenceRegulatory networksMicroarray dataVertebrate evolutionSilencing complexMiRNA functionMiR-19RNA duplexesExpression constructsBioinformatics analysisMature miRNAsStrand speciesVertebratesSpeciesObligate intermediateSensor assayMutagenesis testsRepressionSeed sites
2009
Genetic dissection of the miR-17∼92 cluster of microRNAs in Myc-induced B-cell lymphomas
Mu P, Han Y, Betel D, Yao E, Squatrito M, Ogrodowski P, de Stanchina E, D'Andrea A, Sander C, Ventura A. Genetic dissection of the miR-17∼92 cluster of microRNAs in Myc-induced B-cell lymphomas. Genes & Development 2009, 23: 2806-2811. PMID: 20008931, PMCID: PMC2800095, DOI: 10.1101/gad.1872909.Peer-Reviewed Original ResearchConceptsMiR-17MiR-17~92 clusterMiR-19Computational target predictionMiR-19aTranscriptional target of c-MycMiR-19bTarget of c-MycMiR-17~92Cluster of microRNAsMyc-driven B-cell lymphomasConditional knockout alleleMouse model of B-cell lymphomaGene expression profilesGenetic dissectionIndividual miRNAsMiRNAsProsurvival activityTranscriptional targetsTarget predictionModel of B-cell lymphomaC-mycSuppressed apoptosisMicroRNAsExpression profiles
2007
Valproic acid sodium inhibits the morphine-induced conditioned place preference in the central nervous system of rats
Mu P, Yu L. Valproic acid sodium inhibits the morphine-induced conditioned place preference in the central nervous system of rats. Neuroscience Letters 2007, 426: 135-138. PMID: 17904288, DOI: 10.1016/j.neulet.2007.04.017.Peer-Reviewed Original ResearchConceptsMorphine-induced conditioned place preferenceConditioned place preferenceConditioned place aversionValproic acid sodiumPlace preferenceInjection of morphinePotential therapeutic medicationsPlace aversionCPP modelChronic pretreatmentCentral nervous system of ratsNervous system of ratsDrug abuseSystem of ratsCentral nervous systemRat modelAntiepileptic drugsRatsTherapeutic medicationsIntracerebroventricularI.c.vAbuseDrugMorphineAversion