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 SYNCRIP unleashes APOBEC-driven mutagenesis, tumor heterogeneity, and AR-targeted therapy resistance in prostate cancer
Li X, Wang Y, Deng S, Zhu G, Wang C, Johnson N, Zhang Z, Tirado C, Xu Y, Metang L, Gonzalez J, Mukherji A, Ye J, Yang Y, Peng W, Tang Y, Hofstad M, Xie Z, Yoon H, Chen L, Liu X, Chen S, Zhu H, Strand D, Liang H, Raj G, He H, Mendell J, Li B, Wang T, Mu P. Loss of SYNCRIP unleashes APOBEC-driven mutagenesis, tumor heterogeneity, and AR-targeted therapy resistance in prostate cancer. Cancer Cell 2023, 41: 1427-1449.e12. PMID: 37478850, PMCID: PMC10530398, DOI: 10.1016/j.ccell.2023.06.010.Peer-Reviewed Original ResearchConceptsProstate cancerTherapy resistanceTumor heterogeneityTumor mutational burdenCell-intrinsic mechanismsPromote tumor heterogeneityMutational burdenTargeted therapyDriver mutationsPCa cellsCancer cellsHuman cancersMutated genesCancerMutational signaturesProstateTumorTherapyFOXA1APOBEC proteinsAPOBEC3BEP300Molecular brakeMutationsSYNCRIPSOX2 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
2021
Overcoming oncogene addiction in breast and prostate cancers: a comparative mechanistic overview.
Blatt E, Kopplin N, Kumar S, Mu P, Conzen S, Raj G. Overcoming oncogene addiction in breast and prostate cancers: a comparative mechanistic overview. Endocrine Related Cancer 2021, 28: r31-r46. PMID: 33263560, PMCID: PMC8218927, DOI: 10.1530/erc-20-0272.Peer-Reviewed Original ResearchConceptsProstate cancerHormone-dependent cancersBreast cancerTherapy resistanceAndrogen receptorMechanisms of endocrine therapy resistanceTherapeutic strategiesTherapy-resistant prostate cancerEndocrine therapy resistanceAdvanced prostate cancerTherapy-resistant tumorsNuclear receptorsMechanisms of resistancePotential therapeutic strategyEndocrine therapyMetastatic patientsAntiestrogen resistanceOncogene addictionClinical benefitTumor typesEstrogen receptorFrequent mechanismCancerReceptorsAugmented activity
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
2015
Targeting Breast Cancer Metastasis
Jin X, Mu P. Targeting Breast Cancer Metastasis. Breast Cancer Basic And Clinical Research 2015, 9s1: bcbcr.s25460. PMID: 26380552, PMCID: PMC4559199, DOI: 10.4137/bcbcr.s25460.Peer-Reviewed Original Research