2021
AP-2alpha-mediated activation of E2F and EZH2 drives melanoma metastasis
White J, Thompson D, Koch K, Kiriazov B, Beck A, van der Heide D, Grimm B, Kulak M, Weigel R. AP-2alpha-mediated activation of E2F and EZH2 drives melanoma metastasis. Cancer Research 2021, 81: canres.0772.2021. PMID: 34210752, PMCID: PMC8416798, DOI: 10.1158/0008-5472.can-21-0772.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex 2Adaptor Protein Complex alpha SubunitsAnimalsBase SequenceBenzamidesBiomarkersBiphenyl CompoundsCell Line, TumorE2F Transcription FactorsEnhancer of Zeste Homolog 2 ProteinEpigenesis, GeneticHumansMelanocytesMelanomaMiceMice, Inbred NODMice, SCIDMorpholinesNeoplasm MetastasisNeoplasm TransplantationNeoplasms, Second PrimaryPromoter Regions, GeneticPyridonesSingle-Cell AnalysisTranscription Factor AP-2ConceptsAP-2αRepression complexEZH2 inhibitorsAP-2α transcription factorSingle-cell RNA sequencing analysisE2F target genesRNA sequencing analysisSpecific EZH2 inhibitorsAP-2α expressionActivation of E2FAnchorage-independent colony formationMelanocyte stem cellsTumor suppressor activityChromatin marksNucleosome remodelingBioID screenE2F pathwayTranscriptional activationTranscription factorsTarget genesPathway genesAP-2alphaSequencing analysisMelanoma metastasesGenesAP-2α Regulates S-Phase and Is a Marker for Sensitivity to PI3K Inhibitor Buparlisib in Colon Cancer
Beck AC, Cho E, White JR, Paemka L, Li T, Gu VW, Thompson DT, Koch KE, Franke C, Gosse M, Wu VT, Landers SR, Pamatmat AJ, Kulak MV, Weigel RJ. AP-2α Regulates S-Phase and Is a Marker for Sensitivity to PI3K Inhibitor Buparlisib in Colon Cancer. Molecular Cancer Research 2021, 19: 1156-1167. PMID: 33753551, PMCID: PMC8254761, DOI: 10.1158/1541-7786.mcr-20-0867.Peer-Reviewed Original ResearchMeSH KeywordsAminopyridinesAnimalsBiomarkers, TumorCell Line, TumorCell SurvivalColonic NeoplasmsGene Expression ProfilingGene Expression Regulation, NeoplasticGene Knockout TechniquesHCT116 CellsHumansMiceMorpholinesPhosphoinositide-3 Kinase InhibitorsRNA InterferenceRNA-SeqS PhaseTranscription Factor AP-2Xenograft Model Antitumor AssaysConceptsAP-2αPI3K inhibitorsColon cancer cell linesCell cycleS phasePrimary gene targetsK inhibitorsChromatin immunoprecipitation sequencingCancer cell linesPI3K cascadeProlonged S phaseCell linesActivation of AktShort hairpin RNAPhosphorylation of AktHistone H3Immunoprecipitation sequencingRNA sequencingPI3K inhibitionTarget genesK cascadeGene targetsTumor suppressorHairpin RNAColon cancer
2020
AP-2γ Is Required for Maintenance of Multipotent Mammary Stem Cells
Gu VW, Cho E, Thompson DT, Cassady VC, Borcherding N, Koch KE, Wu VT, Lorenzen AW, van der Heide DM, White JR, Kulak MV, Williams T, Zhang W, Weigel RJ. AP-2γ Is Required for Maintenance of Multipotent Mammary Stem Cells. Stem Cell Reports 2020, 16: 106-119. PMID: 33382976, PMCID: PMC7897584, DOI: 10.1016/j.stemcr.2020.12.002.Peer-Reviewed Original ResearchConceptsMammary stem cellsAP-2γMultipotent mammary stem cellsMammary gland ductal morphogenesisAP-2γ transcription factorMammary gland structureMammary gland developmentStem cellsMammary epithelial cellsAdult MaSCsBasal epitheliumDuctal outgrowthMammary developmentLuminal progenitorsConditional knockoutEpithelial cellsLuminal lineageMammary lineageDuctal morphogenesisGland developmentNumber of cellsRegenerative capacityGland structureExpression of genesCellsA TFAP2C Gene Signature Is Predictive of Outcome in HER2-Positive Breast Cancer
Wu VT, Kiriazov B, Koch KE, Gu VW, Beck AC, Borcherding N, Li T, Addo P, Wehrspan ZJ, Zhang W, Braun TA, Brown BJ, Band V, Band H, Kulak MV, Weigel RJ. A TFAP2C Gene Signature Is Predictive of Outcome in HER2-Positive Breast Cancer. Molecular Cancer Research 2020, 18: 46-56. PMID: 31619506, PMCID: PMC6942205, DOI: 10.1158/1541-7786.mcr-19-0359.Peer-Reviewed Original ResearchConceptsBreast cancerGene signatureAP-2γHER2-positive breast cancerOutcomes of patientsExpression of estrogenSubset of patientsLuminal breast cancerSubset of HER2AP-2γ transcription factorBreast cancer subtypesPathway analysisPhysiologic effectsClinical relevanceCancer growthHER2Hormone responseCancer subtypesDifferent HER2CancerPatientsRetinoic acid pathwayCancer linesOutcomesCell lines