2024
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 programs
2022
Ectopic JAK–STAT activation enables the transition to a stem-like and multilineage state conferring AR-targeted therapy resistance
Deng S, Wang C, Wang Y, Xu Y, Li X, Johnson N, Mukherji A, Lo U, Xu L, Gonzalez J, Metang L, Ye J, Tirado C, Rodarte K, Zhou Y, Xie Z, Arana C, Annamalai V, Liu X, Vander Griend D, Strand D, Hsieh J, Li B, Raj G, Wang T, Mu P. Ectopic JAK–STAT activation enables the transition to a stem-like and multilineage state conferring AR-targeted therapy resistance. Nature Cancer 2022, 3: 1071-1087. PMID: 36065066, PMCID: PMC9499870, DOI: 10.1038/s43018-022-00431-9.Peer-Reviewed Original ResearchConceptsJAK-STAT activationJanus kinase (JAK)-signal transducerTherapy resistanceLineage plasticityTranscriptional programsJAK-STATAR-targeted therapiesLineage programsLineagesMolecular mechanismsTranscriptomic aberrationsPharmaceutical inhibitionProstate cancerTargeted therapyStem-likeTherapeutic targetTherapy
2020
Abstract NG06: CHD1-loss confers AR targeted therapy resistance via promoting cancer heterogeneity and lineage plasticity
Zhang Z, Zhou C, Li X, Barnes S, Deng S, Hoover E, Chen C, Lee Y, Wang C, Tirado C, Metang L, Johnson N, Wongvipat J, Navrazhina K, Cao Z, Abida W, Lujambio A, Li S, Malladi V, Sawyers C, Mu P. Abstract NG06: CHD1-loss confers AR targeted therapy resistance via promoting cancer heterogeneity and lineage plasticity. Cancer Research 2020, 80: ng06-ng06. DOI: 10.1158/1538-7445.am2020-ng06.Peer-Reviewed Original ResearchMetastatic prostate cancerLineage plasticityAndrogen receptorResistance to ARShort hairpin RNAEpithelial to mesenchymal transitionChromodomain helicase DNA-binding protein 1Genomic alterationsCHD1 lossCancer heterogeneityProstate cancerClinical successTumor cellsLuminal prostate epithelial cellsProstate cancer cell line modelsWeeks of xenograftingTargetable driver mutationsCancer cell line modelsResistance to enzalutamideAR target genesProstate epithelial cellsProstate tumor cellsHuman prostate cancerProstate cancer heterogeneityAmerican Association for Cancer Research