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
2023
Loss 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 brakeMutationsSYNCRIP
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