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 programsSOX2 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
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