Featured Publications
Phosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma
Tworkoski K, Singhal G, Szpakowski S, Zito CI, Bacchiocchi A, Muthusamy V, Bosenberg M, Krauthammer M, Halaban R, Stern DF. Phosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma. Molecular Cancer Research 2011, 9: 801-812. PMID: 21521745, PMCID: PMC3117976, DOI: 10.1158/1541-7786.mcr-10-0512.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCell Line, TumorCell MovementCell ProliferationErbB ReceptorsGene Expression Regulation, NeoplasticGene Knockdown TechniquesHEK293 CellsHumansInfant, NewbornMelanocytesMelanomaPhosphoproteinsPhosphorylationProteomicsReceptor Protein-Tyrosine KinasesReceptor, IGF Type 2RNA, Small InterferingSignal TransductionSkin NeoplasmsSTAT3 Transcription FactorConceptsTherapeutic targetReceptor tyrosine kinasesMelanoma cellsPotential therapeutic targetIdentifies potential therapeutic targetsActive receptor tyrosine kinasesTyrosine kinaseMelanoma cell migrationReceptor expressionBreast cancerAxl knockdownAutocrine circuitTherapeutic interventionsCancer subtypesReceptor tyrosine kinase activationTyrosine kinase activationNovel targetActivated receptorsAxlRNA knockdownMelanomaCell migrationHER3KnockdownIGF1R
2020
Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition
Gale M, Li Y, Cao J, Liu ZZ, Holmbeck MA, Zhang M, Lang SM, Wu L, Do Carmo M, Gupta S, Aoshima K, DiGiovanna MP, Stern DF, Rimm DL, Shadel GS, Chen X, Yan Q. Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition. Cancer Research 2020, 80: 524-535. PMID: 31690671, PMCID: PMC7002225, DOI: 10.1158/0008-5472.can-18-3985.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBreast NeoplasmsCell ProliferationDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHumansMiceMice, Inbred NODMice, SCIDMitochondrial Proton-Translocating ATPasesOligomycinsReceptor, ErbB-2TrastuzumabTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsResistant cellsHER2-Targeted TherapyTrastuzumab-resistant tumorsNew therapeutic strategiesNovel potential targetDrug-free mediumAntibody therapySynthase inhibitionLow doseTherapeutic strategiesTrastuzumabBreast tumorsHER2TherapyAcquired ResistanceTumorsPotential targetMitochondrial respirationCellsSelective dependencyInhibitionMinimal changesNovel vulnerabilitiesATP synthase inhibitionOligomycin A
2018
Inhibition of isoprenylation synergizes with MAPK blockade to prevent growth in treatment‐resistant melanoma, colorectal, and lung cancer
Theodosakis N, Langdon CG, Micevic G, Krykbaeva I, Means RE, Stern DF, Bosenberg MW. Inhibition of isoprenylation synergizes with MAPK blockade to prevent growth in treatment‐resistant melanoma, colorectal, and lung cancer. Pigment Cell & Melanoma Research 2018, 32: 292-302. PMID: 30281931, PMCID: PMC6590911, DOI: 10.1111/pcmr.12742.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationColorectal NeoplasmsDrug Resistance, NeoplasmDrug SynergismHumansHydroxymethylglutaryl-CoA Reductase InhibitorsLung NeoplasmsMaleMelanomaMevalonic AcidMice, NudeMitogen-Activated Protein KinasesPrenylationProtein Kinase InhibitorsProtein Processing, Post-TranslationalSignal TransductionConceptsUseful adjunctive therapyHMG-CoA reductase inhibitorsAnti-tumor effectsAdjunctive therapyInhibition of isoprenylationLung cancerMEK inhibitionReductase inhibitorsMAPK blockadeDriver mutationsAdditional studiesStatinsTherapyMelanomaTumorsVemurafenibMAPK pathwayDownstream metabolitesInhibitionMAPKAdjunctiveColorectalSelumetinibBlockadeCancer
2017
p90RSK Blockade Inhibits Dual BRAF and MEK Inhibitor-Resistant Melanoma by Targeting Protein Synthesis
Theodosakis N, Micevic G, Langdon CG, Ventura A, Means R, Stern DF, Bosenberg MW. p90RSK Blockade Inhibits Dual BRAF and MEK Inhibitor-Resistant Melanoma by Targeting Protein Synthesis. Journal Of Investigative Dermatology 2017, 137: 2187-2196. PMID: 28599981, PMCID: PMC6342201, DOI: 10.1016/j.jid.2016.12.033.Peer-Reviewed Original ResearchConceptsProtein synthesisRibosomal S6 kinase (RSK) familyPatient-derived melanoma cell linesDifferential protein expressionReverse phase protein arrayPhase protein arrayTranslation complexesKinase familyBI-D1870RSK inhibitorsMelanoma cell linesProtein arraysCell proliferationInhibitor treatmentProtein expressionCell linesNew targetsHuman melanoma patientsBRAF inhibitor vemurafenibCombinatorial Screening of Pancreatic Adenocarcinoma Reveals Sensitivity to Drug Combinations Including Bromodomain Inhibitor Plus Neddylation Inhibitor
Langdon CG, Platt JT, Means RE, Iyidogan P, Mamillapalli R, Klein M, Held MA, Lee JW, Koo JS, Hatzis C, Hochster HS, Stern DF. Combinatorial Screening of Pancreatic Adenocarcinoma Reveals Sensitivity to Drug Combinations Including Bromodomain Inhibitor Plus Neddylation Inhibitor. Molecular Cancer Therapeutics 2017, 16: 1041-1053. PMID: 28292938, PMCID: PMC5457712, DOI: 10.1158/1535-7163.mct-16-0794.Peer-Reviewed Original ResearchAdenosine TriphosphateAnimalsAntineoplastic AgentsApoptosisCarcinoma, Pancreatic DuctalCell Line, TumorCell ProliferationDNA DamageDose-Response Relationship, DrugDrug CombinationsDrug Screening Assays, AntitumorDrug SynergismHigh-Throughput Nucleotide SequencingHumansMiceMitochondriaMolecular Targeted TherapyNeoplastic Stem CellsPancreatic NeoplasmsSuperoxidesXenograft Model Antitumor AssaysSystematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer
Wali VB, Langdon CG, Held MA, Platt JT, Patwardhan GA, Safonov A, Aktas B, Pusztai L, Stern DF, Hatzis C. Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer. Cancer Research 2017, 77: 566-578. PMID: 27872098, PMCID: PMC5582957, DOI: 10.1158/0008-5472.can-16-1901.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerTNBC cell linesPairwise drug combinationsClinical translationAggressive diseaseCombination therapyBreast cancerPreclinical proofDrug combinationsCombination treatmentInvestigational drugsSingle agentSensitivity patternCell sensitivityCell linesTherapyApoptotic activityAnticancer activityDownregulated genesMitogenic signalingCrizotinibBlockadeClinicAgentsCancer
2016
PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer
Jeong J, VanHouten JN, Dann P, Kim W, Sullivan C, Yu H, Liotta L, Espina V, Stern DF, Friedman PA, Wysolmerski JJ. PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e282-e290. PMID: 26729871, PMCID: PMC4725473, DOI: 10.1073/pnas.1516138113.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCalciumCarcinogenesisCell Line, TumorCell MembraneCell ProliferationCell SurvivalEndocytosisFemaleFluorescent Antibody TechniqueForkhead Box Protein O1Forkhead Transcription FactorsGene Knockdown TechniquesHSP90 Heat-Shock ProteinsHumansImmunoblottingIntracellular SpaceMammary Neoplasms, AnimalMicePlasma Membrane Calcium-Transporting ATPasesProtein BindingProtein TransportReceptor, ErbB-2Signal TransductionSurvival AnalysisConceptsBreast cancerHigh tumor levelsDegradation of HER2Increases Intracellular CalciumMouse mammary tumor virusBreast cancer cellsMammary tumor virusPMCA2 levelsNeu miceTumor levelsFormation of tumorsHER2 levelsIntracellular calciumTherapeutic targetBreast tumorsHER2Milk calciumExpression correlatesCancerHSP 90Mammary glandCancer cellsTumor virusTumorsCalcium
2015
SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells
Langdon CG, Wiedemann N, Held MA, Mamillapalli R, Iyidogan P, Theodosakis N, Platt JT, Levy F, Vuagniaux G, Wang S, Bosenberg MW, Stern DF. SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells. Oncotarget 2015, 6: 37410-37425. PMID: 26485762, PMCID: PMC4741938, DOI: 10.18632/oncotarget.6138.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisApoptosis Regulatory ProteinsAzepinesAzocinesBenzhydryl CompoundsCamptothecinCell Line, TumorCell ProliferationDocetaxelDose-Response Relationship, DrugDrug SynergismFemaleHumansIrinotecanLung NeoplasmsMice, Inbred BALB CMice, NudeNF-kappa BPaclitaxelSignal TransductionTaxoidsTime FactorsTopoisomerase InhibitorsTriazolesTumor BurdenXenograft Model Antitumor AssaysConceptsLung adenocarcinoma cellsDebio 1143Adenocarcinoma cellsOngoing clinical trialsNon-canonical NF-κB signalingTopoisomerase inhibitorsLung adenocarcinoma xenograftsNF-κB signalingBromodomain inhibitor JQ1Clinical trialsConventional chemotherapyTumor volumeVivo treatmentAdenocarcinoma xenograftsAnti-apoptotic proteinsSingle agentCaspase-8 expressionVivo growthInhibitor JQ1Tumor cellsPro-apoptotic protein SmacJQ1Cell linesInhibitorsTaxanesThe broad‐spectrum receptor tyrosine kinase inhibitor dovitinib suppresses growth of BRAF‐mutant melanoma cells in combination with other signaling pathway inhibitors
Langdon CG, Held MA, Platt JT, Meeth K, Iyidogan P, Mamillapalli R, Koo AB, Klein M, Liu Z, Bosenberg MW, Stern DF. The broad‐spectrum receptor tyrosine kinase inhibitor dovitinib suppresses growth of BRAF‐mutant melanoma cells in combination with other signaling pathway inhibitors. Pigment Cell & Melanoma Research 2015, 28: 417-430. PMID: 25854919, PMCID: PMC5215495, DOI: 10.1111/pcmr.12376.Peer-Reviewed Original ResearchConceptsBRAF-mutant melanomaBRAF inhibitorsCell linesCombination of dovitinibBRAF inhibitor treatmentBRAF mutant melanoma cellsBRAF inhibitor resistanceColorectal carcinoma cell linesBRAF-mutant melanoma cell linesMelanoma cell linesCarcinoma cell linesMetastatic melanomaEffective therapyWild-type BRAF cellsInhibitor treatmentAgent inhibitsPathway inhibitorDovitinibInhibitor resistanceMelanoma cellsMelanomaSecond agentInhibitorsTreatment
2014
Convergent and Divergent Cellular Responses by ErbB4 Isoforms in Mammary Epithelial Cells
Wali VB, Haskins JW, Gilmore-Hebert M, Platt JT, Liu Z, Stern DF. Convergent and Divergent Cellular Responses by ErbB4 Isoforms in Mammary Epithelial Cells. Molecular Cancer Research 2014, 12: 1140-1155. PMID: 24829397, PMCID: PMC4728083, DOI: 10.1158/1541-7786.mcr-13-0637.Peer-Reviewed Original ResearchConceptsYAP/Hippo pathwayIsogenic MCF10A cellsMultiple structural isoformsAlternative mRNA splicingDivergent cellular responsesChIP-seq experimentsProteases/protease inhibitorsErbB4 isoformsMammary epithelial cellsAssociation of ErbB4Hippo pathwayMRNA splicingNovel molecular targetsTranscriptional profilingDivergent functionsTranscription factorsCYT-1Signaling activitiesMevalonate pathwayCellular responsesLuminal breast cancer cell linesDiverse biologic activitiesMCF10A cellsCYT-2Intracellular isoformsSignificance of glioma-associated oncogene homolog 1 (GLI1)expression in claudin-low breast cancer and crosstalk with the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway
Colavito SA, Zou MR, Yan Q, Nguyen DX, Stern DF. Significance of glioma-associated oncogene homolog 1 (GLI1)expression in claudin-low breast cancer and crosstalk with the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway. Breast Cancer Research 2014, 16: 444. PMID: 25252859, PMCID: PMC4303124, DOI: 10.1186/s13058-014-0444-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBreast NeoplasmsCell Line, TumorCell MovementCell ProliferationClaudinsEpithelial-Mesenchymal TransitionFemaleGene ExpressionHeterocyclic Compounds, 2-RingHumansMice, Inbred NODMice, SCIDNeoplasm TransplantationNeoplastic Stem CellsNF-kappa BPromoter Regions, GeneticProtein BindingReceptor Cross-TalkRNA, MessengerSignal TransductionThiazolesTranscription FactorsZinc Finger Protein GLI1ConceptsGlioma-associated oncogene homolog 1Claudin-low cell linesBreast cancer stem cellsCancer stem cellsOncogene homolog 1Gli1 expressionBreast cancerClaudin-low breast cancer subtypeMetastatic breast cancer stem cellsNFκB pathwayCell linesClaudin-low breast cancerActivated B cells (NF-κB) pathwayClaudin-low subtypeHomolog 1Breast cancer subtypesMarkers of EMTB-cell pathwayNFκB subunit p65Stem cellsMesenchymal-like characteristicsPoor prognosisTreatment optionsOrthotopic xenograftsAggressive type
2013
MERTK controls melanoma cell migration and survival and differentially regulates cell behavior relative to AXL
Tworkoski KA, Platt JT, Bacchiocchi A, Bosenberg M, Boggon TJ, Stern DF. MERTK controls melanoma cell migration and survival and differentially regulates cell behavior relative to AXL. Pigment Cell & Melanoma Research 2013, 26: 527-541. PMID: 23617806, PMCID: PMC3918898, DOI: 10.1111/pcmr.12110.Peer-Reviewed Original ResearchMeSH KeywordsAxl Receptor Tyrosine KinaseC-Mer Tyrosine KinaseCdc42 GTP-Binding ProteinCell Line, TumorCell MovementCell ProliferationCell SurvivalCytophotometryGene Expression ProfilingGene Expression Regulation, NeoplasticHEK293 CellsHumansMelanomaNeoplasm MetastasisOligonucleotide Array Sequence AnalysisPhosphorylationProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSignal TransductionSkin NeoplasmsConceptsCell migrationCell behaviorMelanoma cellsAkt-dependent mannerShRNA-mediated knockdownDifferential cell behaviorDifferent transcriptional signaturesReceptor tyrosine kinase AXLMelanoma cell migrationMelanoma cell proliferationKinase domainTyrosine kinase AXLCell motilityTranscriptional signatureCell survivalColony formationCell proliferationOverexpression of AxlPossible therapeutic targetMelanoma pathogenesisNovel mutationsMerTKAxlTherapeutic targetMutations
2008
ErbB3 is required for ductal morphogenesis in the mouse mammary gland
Jackson-Fisher AJ, Bellinger G, Breindel JL, Tavassoli FA, Booth CJ, Duong JK, Stern DF. ErbB3 is required for ductal morphogenesis in the mouse mammary gland. Breast Cancer Research 2008, 10: r96. PMID: 19019207, PMCID: PMC2656891, DOI: 10.1186/bcr2198.Peer-Reviewed Original ResearchConceptsTerminal end budsMammary fat padEnd budsMammary budBreast cancerFat padDuctal outgrowthMammary glandHER2/neuHuman breast cancerSmooth muscle actinNormal mammary glandSections of glandsMammary ductal treeMouse mammary gland developmentMammary gland developmentErbB3 functionMouse mammary glandRole of ErbB3Lobuloalveolar developmentEpithelial areaErbB2/HER2/NeuPredictive valueMuscle actinTherapeutic resistance