Featured Publications
UBE2J1 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 processLoss 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 analysisTherapySOX2 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
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
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