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 programsUBE2J1 is the E2 ubiquitin-conjugating enzyme regulating androgen receptor degradation and antiandrogen resistance
Rodriguez Tirado C, Wang C, Li X, Deng S, Gonzalez J, Johnson N, Xu Y, Metang L, Sundar Rajan M, Yang Y, Yin Y, Hofstad M, Raj G, Zhang S, Lemoff A, He W, Fan J, Wang Y, Wang T, Mu P. UBE2J1 is the E2 ubiquitin-conjugating enzyme regulating androgen receptor degradation and antiandrogen resistance. Oncogene 2023, 43: 265-280. PMID: 38030789, PMCID: PMC10798893, DOI: 10.1038/s41388-023-02890-5.Peer-Reviewed Original ResearchConceptsAberrant androgen receptorProstate cancerAR ubiquitinationAR degradationAntiandrogen therapyResistance to antiandrogen therapyE2 ubiquitin-conjugating enzymeEnhanced AR signalingAndrogen receptor degradersAR protein levelsProstate cancer patientsUbiquitin-conjugating enzymeResistant tumorsPCa tumorsAR signalingAndrogen receptorAntiandrogen treatmentAntiandrogen resistanceAR proteinReceptor degradationProtein levelsOncogenic proteinsTumorTherapyProtein degradation processSOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer
Mu P, Zhang Z, Benelli M, Karthaus W, Hoover E, Chen C, Wongvipat J, Ku S, Gao D, Cao Z, Shah N, Adams E, Abida W, Watson P, Prandi D, Huang C, de Stanchina E, Lowe S, Ellis L, Beltran H, Rubin M, Goodrich D, Demichelis F, Sawyers C. SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science 2017, 355: 84-88. PMID: 28059768, PMCID: PMC5247742, DOI: 10.1126/science.aah4307.Peer-Reviewed Original ResearchConceptsLineage plasticityRB1 functionHuman prostate cancer modelProstate cancer modelLoss of TP53Basal-like cellsTumor suppressor geneTranscription factor Sox2Antiandrogen therapyProstate cancerInhibiting Sox2 expressionLineage switchAntiandrogen resistanceCancer modelsTumor cellsSuppressor geneSOX2 expressionIncreased expressionTP53TumorCell lineagesCellular plasticityIn vitroPhenotypic shiftCancer
2022
SOX2 mediates metabolic reprogramming of prostate cancer cells
de Wet L, Williams A, Gillard M, Kregel S, Lamperis S, Gutgesell L, Vellky J, Brown R, Conger K, Paner G, Wang H, Platz E, De Marzo A, Mu P, Coloff J, Szmulewitz R, Vander Griend D. SOX2 mediates metabolic reprogramming of prostate cancer cells. Oncogene 2022, 41: 1190-1202. PMID: 35067686, PMCID: PMC8858874, DOI: 10.1038/s41388-021-02157-x.Peer-Reviewed Original ResearchConceptsProstate cancer cellsSOX2 expressionCancer cellsTherapy resistanceMetastatic progressionMetabolic reprogrammingAssociated with multiple oncogenic pathwaysAndrogen-sensitive prostate cancer cellsGene targetingCastration-resistant prostate cancer cellsIncreased spare respiratory capacityChIP-seq analysisRNA-seq datasetsStem cell transcription factor Sox2Prostate cancer cell linesAnnotated tumor specimensSOX2 binding sitesPentose phosphate pathwayCRISPR-mediated deletionDecreased patient survivalSpare respiratory capacityQuantity of mitochondriaDeletion of Sox2Case-control cohortGene expression analysis
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
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 ResearchMeSH KeywordsAnimalsCell Line, TumorGene DeletionGenes, mycLymphoma, B-CellMiceMice, Inbred C57BLMice, NudeMicroRNAsConceptsMiR-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