2024
Hyd/UBR5 defines a tumor suppressor pathway that links Polycomb repressive complex to regulated protein degradation in tissue growth control and tumorigenesis
Wen P, Lei H, Deng H, Deng S, Tirado C, Wang M, Mu P, Zheng Y, Pan D. Hyd/UBR5 defines a tumor suppressor pathway that links Polycomb repressive complex to regulated protein degradation in tissue growth control and tumorigenesis. Genes & Development 2024, 38: 675-691. PMID: 39137945, PMCID: PMC11368183, DOI: 10.1101/gad.351856.124.Peer-Reviewed Original ResearchConceptsPolycomb Repressive Complex1Tumor suppressor pathwayTissue growth controlSuppressor pathwayProtein degradationZinc finger genesGrowth controlUbiquitin-mediated degradationE3 ubiquitin ligasePolycomb repressive complexesProtein degradation pathwaysTumor suppressor geneHyperplastic discsFinger genesMammalian homologSubstrate adaptorRepressive complexesUbiquitin ligaseEmbryonic segmentationProtein complexesModel organismsHuman geneticsUpstream regulatorSuppressor geneProstate cancer tumorigenesisZNF397 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
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 processZNF397 Loss Triggers TET2-driven Epigenetic Rewiring, Lineage Plasticity, and AR-targeted Therapy Resistance in AR-dependent Cancers.
Xu Y, Wang Z, Sjöström M, Deng S, Wang C, Johnson NA, Gonzalez J, Li X, Metang LA, Tirado CR, Mukherji A, Wainwright G, Yu X, Yang Y, Barnes S, Hofstad M, Zhu H, Hanker A, He HH, Chen Y, Wang Z, Raj G, Arteaga C, Feng F, Wang Y, Wang T, Mu P. ZNF397 Loss Triggers TET2-driven Epigenetic Rewiring, Lineage Plasticity, and AR-targeted Therapy Resistance in AR-dependent Cancers. BioRxiv 2023 PMID: 37961351, DOI: 10.1101/2023.10.24.563645.Peer-Reviewed Original ResearchLoss 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 targetTherapyThe driver role of JAK‐STAT signalling in cancer stemness capabilities leading to new therapeutic strategies for therapy‐ and castration‐resistant prostate cancer
Lo U, Chen Y, Cen J, Deng S, Luo J, Zhau H, Ho L, Lai C, Mu P, Chung L, Hsieh J. The driver role of JAK‐STAT signalling in cancer stemness capabilities leading to new therapeutic strategies for therapy‐ and castration‐resistant prostate cancer. Clinical And Translational Medicine 2022, 12: e978. PMID: 35908276, PMCID: PMC9339240, DOI: 10.1002/ctm2.978.Peer-Reviewed Original ResearchConceptsCastration-resistant prostate cancerProstate cancerCancer stem cellsActivation of JAKJAK-STAT signalingGene set enrichment analysisJAK-STAT1 pathwaySTAT1 inhibitorAcquisition of stemness propertiesProstate cancer cell linesProstate cancer stemnessAssociated with cancer stem cellsIn vivo anti-tumor activityMetastatic prostate cancerTumor-initiating capabilityJAK-STATProstasphere assayDownstream effectorsIngenuity PathwayGenetic manipulationCSC genesBioinformatics analysisEnrichment analysisJAK-STAT1Signaling pathway
2020
The actin polymerization factor Diaphanous and the actin severing protein Flightless I collaborate to regulate sarcomere size
Deng S, Silimon R, Balakrishnan M, Bothe I, Juros D, Soffar D, Baylies M. The actin polymerization factor Diaphanous and the actin severing protein Flightless I collaborate to regulate sarcomere size. Developmental Biology 2020, 469: 12-25. PMID: 32980309, PMCID: PMC8279456, DOI: 10.1016/j.ydbio.2020.09.014.Peer-Reviewed Original ResearchConceptsActin thin filamentsFlightless IRegulate thin filament lengthContractile unit of muscleControl actin dynamicsActin polymerization factorsThin filamentsDrosophila flight muscleMyosin thick filamentsThin filament lengthSarcomere sizeActin regulatorsActin dynamicsFlight musclesThick filamentsActinMuscle developmentFilament lengthContractile unitsPolymerization factorsFunction of muscle fibersFilamentsSarcomereRegulationForminAbstract 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 ResearchLoss 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 analysisTherapy
2019
The paracrine induction of prostate cancer progression by caveolin-1
Lin C, Yun E, Lo U, Tai Y, Deng S, Hernandez E, Dang A, Chen Y, Saha D, Mu P, Lin H, Li T, Shen T, Lai C, Hsieh J. The paracrine induction of prostate cancer progression by caveolin-1. Cell Death & Disease 2019, 10: 834. PMID: 31685812, PMCID: PMC6828728, DOI: 10.1038/s41419-019-2066-3.Peer-Reviewed Original ResearchConceptsCastration-resistant prostate cancerCancer stem cellsTumor-derived exosomesProstate cancerCav-1Cancer progressionSubpopulation of cancer stem cellsAssociated with stem cell phenotypeCancer immune evasionProstate cancer progressionStem cell capabilitiesStem cell phenotypePromote cancer developmentPresence of Cav-1Heterogeneous cancer cell populationsCancer cell populationsNeuroendocrine differentiationNeuroendocrine transdifferentiationEpithelial-mesenchymal transitionNFkB signaling pathwayTherapeutic resistanceTumor cellsImmune evasionChemotherapeutic resistanceParacrine induction
2017
Acting on identity: Myoblast fusion and the formation of the syncytial muscle fiber
Deng S, Azevedo M, Baylies M. Acting on identity: Myoblast fusion and the formation of the syncytial muscle fiber. Seminars In Cell And Developmental Biology 2017, 72: 45-55. PMID: 29101004, PMCID: PMC5910025, DOI: 10.1016/j.semcdb.2017.10.033.Peer-Reviewed Original ResearchThe RNA-editing enzyme ADAR promotes lung adenocarcinoma migration and invasion by stabilizing FAK
Amin E, Liu Y, Deng S, Tan K, Chudgar N, Mayo M, Sanchez-Vega F, Adusumilli P, Schultz N, Jones D. The RNA-editing enzyme ADAR promotes lung adenocarcinoma migration and invasion by stabilizing FAK. Science Signaling 2017, 10 PMID: 28928239, PMCID: PMC5771642, DOI: 10.1126/scisignal.aah3941.Peer-Reviewed Original ResearchConceptsFocal adhesion kinaseRNA editing enzyme ADARPresence of ADARsAnalysis of gene expression patternsGenome-wide studiesLung adenocarcinoma cellsRNA-binding proteinsCell migration pathwaysGene expression patternsStabilized transcriptsIntron sitesADARProtein abundanceBinding proteinIncreased abundanceExpression patternsMolecular analysisStage I LUAD patientsPharmacological inhibitionProteinMesenchymal propertiesPotential therapeutic applicationsProtein levelsTranscriptionGenes
2016
Diaphanous regulates SCAR complex localization during Drosophila myoblast fusion
Deng S, Bothe I, Baylies M. Diaphanous regulates SCAR complex localization during Drosophila myoblast fusion. Fly 2016, 10: 178-186. PMID: 27314572, PMCID: PMC5036928, DOI: 10.1080/19336934.2016.1195938.Peer-Reviewed Original ResearchConceptsArp2/3 activationMyoblast fusionFusion siteSCAR activityDrosophila myoblast fusionBranched actin networksRegulate actin dynamicsActin cytoskeletal rearrangementDrosophila to manExtra View articleLoss of SCARCell-cell fusionOrganizing actinActin dynamicsActin rearrangementActin networkCytoskeletal rearrangementsSite of fusionMultinucleated muscle cellsActinComplex localizationDrosophilaWaspsView articleModel system
2015
The Formin Diaphanous Regulates Myoblast Fusion through Actin Polymerization and Arp2/3 Regulation
Deng S, Bothe I, Baylies M. The Formin Diaphanous Regulates Myoblast Fusion through Actin Polymerization and Arp2/3 Regulation. PLOS Genetics 2015, 11: e1005381. PMID: 26295716, PMCID: PMC4546610, DOI: 10.1371/journal.pgen.1005381.Peer-Reviewed Original ResearchConceptsF-actin fociF-actinActin polymerizationCell-cell fusionPodosome formationMyoblast fusionFusion siteElongation of actin filamentsRegulation of actin polymerizationLoss-of-function conditionsActin turnover rateBranched actin regulatorsDrosophila myoblast fusionBranched actin polymerizationPodosome-like structuresF-actin polymerizationF-actin distributionFormation of multinucleated muscle cellsArp2/3 regulatorsBranched actinActin regulatorsActin structuresDynamic filopodiaActin filamentsMutant alleles
2014
Feedback inhibition of ENaC: Acute and chronic mechanisms
Patel A, Yang L, Deng S, Palmer L. Feedback inhibition of ENaC: Acute and chronic mechanisms. Channels 2014, 8: 444-451. PMID: 25483587, PMCID: PMC4594590, DOI: 10.4161/19336950.2014.949190.Peer-Reviewed Original ResearchPI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site
Bothe I, Deng S, Baylies M. PI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site. Journal Of Cell Science 2014, 127: e1-e1. DOI: 10.1242/jcs.157057.Peer-Reviewed Original ResearchPI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site
Bothe I, Deng S, Baylies M. PI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site. Development 2014, 141: 2289-2301. PMID: 24821989, PMCID: PMC4034421, DOI: 10.1242/dev.100743.Peer-Reviewed Original ResearchMeSH KeywordsActin-Related Protein 2-3 ComplexActinsAnimalsCell CommunicationCell MembraneCytoskeletonDrosophila melanogasterGene Expression Regulation, DevelopmentalGenotypeMuscle Fibers, SkeletalMutationMyoblastsPhosphatidylinositol 4,5-DiphosphatePhospholipidsRac GTP-Binding ProteinsSignal TransductionConceptsF-actinRegulation of F-actin dynamicsActivator of actin polymerizationFusion siteF-actin fociMyoblast fusionF-actin dynamicsRegulation of actinCell-cell fusionActin regulatorsActin fociActin remodelingActin polymerizationPhosphoinositide PI(4,5)P2Regulates localizationCytoskeleton signalingOpposing membranesPI(4,5)P2ActinImpaired fusionArp2/3Receptor engagementCytoskeletonRegulationEnrichment
2012
Feedback Inhibition of the epithelial Na+ channel (ENaC): in vitro vs. in vivo
Patel A, Frindt G, Deng S, Palmer L. Feedback Inhibition of the epithelial Na+ channel (ENaC): in vitro vs. in vivo. The FASEB Journal 2012, 26: 867.12-867.12. DOI: 10.1096/fasebj.26.1_supplement.867.12.Peer-Reviewed Original ResearchTwo-electrode voltage clampENaC-expressing oocytesCell surface expressionI NaENaC expressionCell surface expression of ENaCInhibition of ENaCAmiloride-sensitive currentsEpithelial Na+ channelExpression of ENaCCell surfaceFeedback inhibitionIn vivo protocolsNa+ channelsENaCPatch clampVoltage clampInvestigated in vitroRatsOocytesSplit-openOvernight incubationIn vitroHours incubationInhibition
2008
Leaf surface factors of transgenic Bt cotton associated with the feeding behaviors of cotton aphids: A case study on non-target effects
Xue K, Deng S, Wang R, Yan F, Xu C. Leaf surface factors of transgenic Bt cotton associated with the feeding behaviors of cotton aphids: A case study on non-target effects. Science China Life Sciences 2008, 51: 145-156. PMID: 18239893, DOI: 10.1007/s11427-008-0028-6.Peer-Reviewed Original ResearchConceptsNon-Bt cotton lineElectrical penetration graphTransgenic Bt cottonCotton linesBt cottonCotton aphidElectrical penetration graph resultsNon-Bt linesNon-target pestsFeeding behaviorLeaf surface extractsLeaf surface chemicalsCotton plantsNon-target effectsAphis gossypiiLeaf factorsLeaf extractAphidsLeafGlandular trichomesCottonTrichomesFeedingRegression equationChemical analysis