2019
Multiplexed (18-Plex) Measurement of Signaling Targets and Cytotoxic T Cells in Trastuzumab-Treated Patients using Imaging Mass Cytometry
Carvajal-Hausdorf DE, Patsenker J, Stanton KP, Villarroel-Espindola F, Esch A, Montgomery RR, Psyrri A, Kalogeras KT, Kotoula V, Foutzilas G, Schalper KA, Kluger Y, Rimm DL. Multiplexed (18-Plex) Measurement of Signaling Targets and Cytotoxic T Cells in Trastuzumab-Treated Patients using Imaging Mass Cytometry. Clinical Cancer Research 2019, 25: 3054-3062. PMID: 30796036, PMCID: PMC6522272, DOI: 10.1158/1078-0432.ccr-18-2599.Peer-Reviewed Original ResearchConceptsTrastuzumab-treated patientsT cell infiltrationCD8 T cell infiltrationCohort of patientsCytotoxic T cellsMass cytometryCase-control seriesExtracellular domainMechanism of actionTrastuzumab benefitAdjuvant treatmentCD8 cellsRecurrence eventsT cellsAntibody panelImmune systemPatientsMetal-conjugated antibodiesQuantitative immunofluorescenceTrastuzumabImaging Mass CytometryHER2Signaling targetsObjective measurementsCytometry
2017
Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer
Gettinger S, Choi J, Hastings K, Truini A, Datar I, Sowell R, Wurtz A, Dong W, Cai G, Melnick MA, Du VY, Schlessinger J, Goldberg SB, Chiang A, Sanmamed MF, Melero I, Agorreta J, Montuenga LM, Lifton R, Ferrone S, Kavathas P, Rimm DL, Kaech SM, Schalper K, Herbst RS, Politi K. Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer. Cancer Discovery 2017, 7: cd-17-0593. PMID: 29025772, PMCID: PMC5718941, DOI: 10.1158/2159-8290.cd-17-0593.Peer-Reviewed Original ResearchMeSH KeywordsDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHistocompatibility Antigens Class IHumansLung NeoplasmsSignal TransductionConceptsImmune checkpoint inhibitorsPatient-derived xenograftsHLA class ILung cancerClass ICell surface HLA class ILung cancer mouse modelPD-1 blockadeStandard treatment algorithmCancer mouse modelLung cancer samplesDefective antigen processingCheckpoint inhibitorsPD-1Treatment algorithmMouse modelAntagonistic antibodiesDiverse malignanciesAntigen processingCancer samplesB2MHomozygous lossTumorsCancerRecurrent mutationsErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC
Alvarado D, Ligon GF, Lillquist JS, Seibel SB, Wallweber G, Neumeister VM, Rimm DL, McMahon G, LaVallee TM. ErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC. PLOS ONE 2017, 12: e0181356. PMID: 28723928, PMCID: PMC5517012, DOI: 10.1371/journal.pone.0181356.Peer-Reviewed Original ResearchConceptsNeuregulin-1NRG1 expressionErbB3 activationNeck squamous cell carcinomaSquamous cell carcinomaEnhanced anti-tumor activitySubset of HNSCCUnmet medical needHNSCC cell linesHNSCC patient samplesAnti-tumor activityGrowth factor αLigand neuregulin-1Cell carcinomaEGFR/ErbB familyHNSCC modelsCetuximab treatmentErbB receptor inhibitionReceptor inhibitionReceptor levelsRespective signaling pathwaysSolid tumorsTumor typesHNSCCPotential biomarkers
2016
Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence
Balko JM, Schwarz LJ, Luo N, Estrada MV, Giltnane JM, Dávila-González D, Wang K, Sánchez V, Dean PT, Combs SE, Hicks D, Pinto JA, Landis MD, Doimi FD, Yelensky R, Miller VA, Stephens PJ, Rimm DL, Gómez H, Chang JC, Sanders ME, Cook RS, Arteaga CL. Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence. Science Translational Medicine 2016, 8: 334ra53. PMID: 27075627, PMCID: PMC5256931, DOI: 10.1126/scitranslmed.aad3001.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsCell Line, TumorCell ProliferationChromosomes, Human, Pair 9Cohort StudiesFemaleGene AmplificationGene Knockdown TechniquesGenetic LociHumansJanus Kinase 2Middle AgedSignal TransductionSpheroids, CellularSTAT3 Transcription FactorSTAT6 Transcription FactorTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerJAK2 amplificationBreast cancerUntreated triple-negative breast cancerEventual metastatic spreadBasal-like cancersBreast cancer subtypesTNBC cell linesAmplification of JAK2Janus kinase 2 (JAK2) geneNeoadjuvant chemotherapyOverall survivalTNBC xenograftsJAK1/2 inhibitorClinical trialsMetastatic spreadKinase 2 geneJAK2-specific inhibitorTumor growthCancer subtypesMammosphere formationPatientsPotential biomarkersTumor progressionJAK2 inhibitorsRAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors
Loi S, Dushyanthen S, Beavis PA, Salgado R, Denkert C, Savas P, Combs S, Rimm DL, Giltnane JM, Estrada MV, Sánchez V, Sanders ME, Cook RS, Pilkinton MA, Mallal SA, Wang K, Miller VA, Stephens PJ, Yelensky R, Doimi FD, Gómez H, Ryzhov SV, Darcy PK, Arteaga CL, Balko JM. RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors. Clinical Cancer Research 2016, 22: 1499-1509. PMID: 26515496, PMCID: PMC4794351, DOI: 10.1158/1078-0432.ccr-15-1125.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB7-H1 AntigenBiomarkersCell Line, TumorDisease Models, AnimalDisease ProgressionFemaleGene Expression ProfilingHumansImmunomodulationImmunophenotypingLymphocytes, Tumor-InfiltratingMiceMitogen-Activated Protein KinasesMortalityPhenotypeProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsRas ProteinsSignal TransductionTranscriptomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerTumor-infiltrating lymphocytesImmune checkpoint inhibitorsResidual diseaseNeoadjuvant chemotherapyBreast cancerPD-L1Checkpoint inhibitorsMHC expressionMouse modelPD-1/PD-L1 immune checkpoint inhibitorsPD-L1 immune checkpoint inhibitorsPresence of TILsPD-1/PD-L1Low tumor-infiltrating lymphocytesPD-L1/PDAntitumor immune responseRAS/MAPK activationCell-surface MHC expressionMAPK activationImproved survivalImproved prognosisPredictive biomarkersClinical trialsImmune response
2015
Regulation of Glutamine Carrier Proteins by RNF5 Determines Breast Cancer Response to ER Stress-Inducing Chemotherapies
Jeon YJ, Khelifa S, Ratnikov B, Scott DA, Feng Y, Parisi F, Ruller C, Lau E, Kim H, Brill LM, Jiang T, Rimm DL, Cardiff RD, Mills GB, Smith JW, Osterman AL, Kluger Y, Ronai Z. Regulation of Glutamine Carrier Proteins by RNF5 Determines Breast Cancer Response to ER Stress-Inducing Chemotherapies. Cancer Cell 2015, 27: 354-369. PMID: 25759021, PMCID: PMC4356903, DOI: 10.1016/j.ccell.2015.02.006.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid Transport System AAmino Acid Transport System ASCAnimalsAntineoplastic AgentsApoptosisAutophagyBreast NeoplasmsCitric Acid CycleDNA-Binding ProteinsEndoplasmic ReticulumEndoplasmic Reticulum StressFemaleHumansMice, Inbred BALB CMice, Inbred C57BLMice, NudeMinor Histocompatibility AntigensPaclitaxelProteolysisSignal TransductionTOR Serine-Threonine KinasesUbiquitin-Protein LigasesUbiquitinationConceptsBreast cancerPyMT mammary tumorsTCA cycle componentsBreast cancer responseMDA-MB-231 cellsSLC1A5 expressionMammary tumorsCancer responseGlutamine dependencePositive prognosisER stressCell deathAltered metabolismTumor cellsCarrier proteinPaclitaxel responsivenessGln uptakeChemotherapyCycle componentsRegulationExpressionUbiquitinationCellsPrognosis
2014
Prognostic Biomarkers in Phase II Trial of Cetuximab-Containing Induction and Chemoradiation in Resectable HNSCC: Eastern Cooperative Oncology Group E2303
Psyrri A, Lee JW, Pectasides E, Vassilakopoulou M, Kosmidis EK, Burtness BA, Rimm DL, Wanebo HJ, Forastiere AA. Prognostic Biomarkers in Phase II Trial of Cetuximab-Containing Induction and Chemoradiation in Resectable HNSCC: Eastern Cooperative Oncology Group E2303. Clinical Cancer Research 2014, 20: 3023-3032. PMID: 24700741, PMCID: PMC4049169, DOI: 10.1158/1078-0432.ccr-14-0113.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarboplatinCarcinoma, Squamous CellCetuximabChemoradiotherapyDisease-Free SurvivalDrug Resistance, NeoplasmFemaleFluorescent Antibody TechniqueHead and Neck NeoplasmsHumansInduction ChemotherapyKaplan-Meier EstimateMaleMiddle AgedMitogen-Activated Protein Kinase KinasesPaclitaxelPhosphatidylinositol 3-KinasesPrognosisProportional Hazards ModelsProto-Oncogene Proteins c-aktRas ProteinsSignal TransductionSquamous Cell Carcinoma of Head and NeckTissue Array AnalysisConceptsProgression-free survivalEvent-free survivalPhase II trialOverall survivalII trialTissue microarrayStage III/IV headMultivariable Cox proportional hazards modelsMultivariable Cox regression analysisNeck squamous cell cancerRAS/MAPK/ERKCox proportional hazards modelInsulin-like growth factor 1 receptorLarge prospective studiesCox regression analysisInferior overall survivalKaplan-Meier methodSquamous cell cancerLog-rank testGrowth factor 1 receptorProportional hazards modelPI3K/Akt pathwayFactor 1 receptorPI3K/AktEGF receptor
2012
Hypoxia-induced protein CAIX is associated with somatic loss of BRCA1 protein and pathway activity in triple negative breast cancer
Neumeister VM, Sullivan CA, Lindner R, Lezon-Geyda K, Li J, Zavada J, Martel M, Glazer PM, Tuck DP, Rimm DL, Harris L. Hypoxia-induced protein CAIX is associated with somatic loss of BRCA1 protein and pathway activity in triple negative breast cancer. Breast Cancer Research And Treatment 2012, 136: 67-75. PMID: 22976806, DOI: 10.1007/s10549-012-2232-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigens, NeoplasmBiomarkers, TumorBRCA1 ProteinBreast NeoplasmsCarbonic Anhydrase IXCarbonic AnhydrasesCell HypoxiaFemaleGene Expression Regulation, NeoplasticHumansMiddle AgedMutationNeoplasm StagingReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSignal TransductionConceptsTriple-negative breast cancerCA IX protein expressionNegative breast cancerBreast cancer cohortTNBC cohortProtein expressionBreast cancerCancer cohortCA IXTriple-negative patientsWorse overall survivalBreast cancer patientsTriple-negative phenotypePARP inhibitor therapyUnselected breast cancer cohortGene expression signaturesInhibitor therapyNegative patientsOverall survivalUnselected cohortCancer patientsBRCA1 protein expressionUseful biomarkerPatientsDefective homologous recombinationmicroRNA Regulatory Network Inference Identifies miR-34a as a Novel Regulator of TGF-β Signaling in Glioblastoma
Genovese G, Ergun A, Shukla SA, Campos B, Hanna J, Ghosh P, Quayle SN, Rai K, Colla S, Ying H, Wu CJ, Sarkar S, Xiao Y, Zhang J, Zhang H, Kwong L, Dunn K, Wiedemeyer WR, Brennan C, Zheng H, Rimm DL, Collins JJ, Chin L. microRNA Regulatory Network Inference Identifies miR-34a as a Novel Regulator of TGF-β Signaling in Glioblastoma. Cancer Discovery 2012, 2: 736-749. PMID: 22750848, PMCID: PMC3911772, DOI: 10.1158/2159-8290.cd-12-0111.Peer-Reviewed Original ResearchConceptsMultidimensional cancer genomic dataPromoter enrichment analysisCancer genomic dataNovel regulatorGenomic dataContext likelihoodEnrichment analysisPutative regulatory networksFunctional genetic screensDifferent genetic elementsGenetic screenTGF-β signalingTranscriptional networksPlatelet-derived growth factorMRNA nodesGenome spaceRegulatory networksTranscriptomic networksBiology of cancerNovel regulationGenetic elementsTumor suppressorSilico analysisDirect regulationNew pathogenetic insightsMulti-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells
Zito CR, Jilaveanu LB, Anagnostou V, Rimm D, Bepler G, Maira SM, Hackl W, Camp R, Kluger HM, Chao HH. Multi-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells. PLOS ONE 2012, 7: e31331. PMID: 22355357, PMCID: PMC3280285, DOI: 10.1371/journal.pone.0031331.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic AgentsBlotting, WesternCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCell Line, TumorCell ProliferationClass Ia Phosphatidylinositol 3-KinaseDrug SynergismFemaleFluorescent Antibody TechniqueHumansImmunoenzyme TechniquesLung NeoplasmsMaleMiddle AgedPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktSignal TransductionTissue Array AnalysisTOR Serine-Threonine KinasesConceptsNon-small cell lung cancerNSCLC cell linesDual PI3K/mTOR inhibitorPI3K/AKT/mTOR pathwayPI3K/mTOR inhibitorAKT/mTOR pathwayPI3K inhibitorsNVP-BEZ235MTOR inhibitorsNVP-BKM120MTOR expressionAdvanced stageCell linesMTOR pathwayPI3K subunitsNon-small cell lung cancer cellsK inhibitorsCell lung cancer cellsCell lung cancerSquamous cell carcinomaP85 expressionSynergistic growth inhibitionRegulation of pAktExpression of p85Lung cancer cells
2011
β-Catenin Signaling Controls Metastasis in Braf-Activated Pten-Deficient Melanomas
Damsky WE, Curley DP, Santhanakrishnan M, Rosenbaum LE, Platt JT, Rothberg BE, Taketo MM, Dankort D, Rimm DL, McMahon M, Bosenberg M. β-Catenin Signaling Controls Metastasis in Braf-Activated Pten-Deficient Melanomas. Cancer Cell 2011, 20: 741-754. PMID: 22172720, PMCID: PMC3241928, DOI: 10.1016/j.ccr.2011.10.030.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, DifferentiationBenzamidesBeta CateninCell Transformation, NeoplasticColorectal NeoplasmsEnzyme ActivationGene Knockdown TechniquesHumansImatinib MesylateKaplan-Meier EstimateLung NeoplasmsLymphatic MetastasisMelanocytesMelanoma, ExperimentalMiceMice, 129 StrainMice, Inbred C57BLMice, TransgenicPhosphorylationPiperazinesProtein StabilityProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePyrimidinesSignal TransductionSkin NeoplasmsSplenic NeoplasmsTranscription, GeneticTumor Cells, CulturedConceptsΒ-catenin levelsPI3K/AktLymph nodesMetastatic tumorsFrequent metastasisTumor differentiationMalignant melanomaMAPK/ERKMelanoma metastasesMouse modelControl metastasisHuman melanomaMelanomaMetastasisΒ-catenin stabilizationPTEN lossCentral mediatorMetastasis regulatorsΒ-cateninSpecific changesFunctional implicationsWntLungA Pathway for the Control of Anoikis Sensitivity by E-Cadherin and Epithelial-to-Mesenchymal Transition
Kumar S, Park SH, Cieply B, Schupp J, Killiam E, Zhang F, Rimm DL, Frisch SM. A Pathway for the Control of Anoikis Sensitivity by E-Cadherin and Epithelial-to-Mesenchymal Transition. Molecular And Cellular Biology 2011, 31: 4036-4051. PMID: 21746881, PMCID: PMC3187352, DOI: 10.1128/mcb.01342-10.Peer-Reviewed Original ResearchConceptsRegulation of anoikisE-cadherin complexMesenchymal transitionE-cadherinAnoikis sensitivityNuclear localizationInappropriate matrixAnoikis resistanceApoptotic responseOncogenic EMTAnoikisNRAGECellular sensitivityNovel pathwayUnknown mechanismAnkyrinEpithelial cellsEMTPathwayP14ARFCellsTbx2ComplexesGenesCytoplasmTargeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer
Ni M, Chen Y, Lim E, Wimberly H, Bailey ST, Imai Y, Rimm DL, Liu XS, Brown M. Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer. Cancer Cell 2011, 20: 119-131. PMID: 21741601, PMCID: PMC3180861, DOI: 10.1016/j.ccr.2011.05.026.Peer-Reviewed Original ResearchMeSH KeywordsAndrogensAnilidesAnimalsBeta CateninBreast NeoplasmsCell Line, TumorCell ProliferationDihydrotestosteroneFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHepatocyte Nuclear Factor 3-alphaHumansMiceNitrilesReceptor, ErbB-2Receptors, AndrogenReceptors, EstrogenSignal TransductionTosyl CompoundsTranscriptional ActivationUp-RegulationWnt ProteinsXenograft Model Antitumor AssaysConceptsAndrogen receptorBreast cancerEstrogen receptorER-/HER2Estrogen receptor-negative breast cancerReceptor-negative breast cancerBreast cancer growthER- breast tumorsPotential therapeutic approachTumor cell growthAndrogen-regulated gene expressionEndocrine therapyER statusTherapeutic approachesAR cistromeBreast tumorsCancer growthDirect transcriptional inductionCancerHER2Ligand-dependent activationReceptorsSpecific targetingTumorsCell growthGefitinib or Placebo in Combination with Tamoxifen in Patients with Hormone Receptor–Positive Metastatic Breast Cancer: A Randomized Phase II Study
Osborne CK, Neven P, Dirix LY, Mackey JR, Robert J, Underhill C, Schiff R, Gutierrez C, Migliaccio I, Anagnostou VK, Rimm DL, Magill P, Sellers M. Gefitinib or Placebo in Combination with Tamoxifen in Patients with Hormone Receptor–Positive Metastatic Breast Cancer: A Randomized Phase II Study. Clinical Cancer Research 2011, 17: 1147-1159. PMID: 21220480, PMCID: PMC3074404, DOI: 10.1158/1078-0432.ccr-10-1869.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDrug-Related Side Effects and Adverse ReactionsErbB ReceptorsFemaleGefitinibHumansMiddle AgedNeoplasms, Hormone-DependentPlacebosQuinazolinesReceptor, ErbB-2Receptors, EstrogenSignal TransductionTamoxifenTreatment OutcomeConceptsAdjuvant aromatase inhibitorsMetastatic breast cancerBreast cancerHormone receptor-positive metastatic breast cancerPositive metastatic breast cancerRandomized phase II studyRandomized phase II trialClinical benefit ratePhase II studyPhase II trialProgression-free survivalStratum 1Epidermal growth factor receptor inhibitor gefitinibFurther investigationAdjuvant tamoxifenImproved PFSPFS HRAI therapyII studyII trialMetastatic diseaseAppropriate patientsPredictive biomarkersPrimary tumorTamoxifen resistance
2010
Vertical Targeting of the Phosphatidylinositol-3 Kinase Pathway as a Strategy for Treating Melanoma
Aziz SA, Jilaveanu LB, Zito C, Camp RL, Rimm DL, Conrad P, Kluger HM. Vertical Targeting of the Phosphatidylinositol-3 Kinase Pathway as a Strategy for Treating Melanoma. Clinical Cancer Research 2010, 16: 6029-6039. PMID: 21169255, PMCID: PMC3058635, DOI: 10.1158/1078-0432.ccr-10-1490.Peer-Reviewed Original ResearchThe ERα coactivator, HER4/4ICD, regulates progesterone receptor expression in normal and malignant breast epithelium
Rokicki J, Das PM, Giltnane JM, Wansbury O, Rimm DL, Howard BA, Jones FE. The ERα coactivator, HER4/4ICD, regulates progesterone receptor expression in normal and malignant breast epithelium. Molecular Cancer 2010, 9: 150. PMID: 20550710, PMCID: PMC2894764, DOI: 10.1186/1476-4598-9-150.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell Line, TumorErbB ReceptorsEstrogen Receptor alphaFemaleGene ExpressionGene Expression RegulationHumansMammary Glands, AnimalMammary Glands, HumanMiceMice, TransgenicPregnancyReceptor, ErbB-4Receptors, ProgesteroneReverse Transcriptase Polymerase Chain ReactionSignal TransductionConceptsPgR expressionExpression of PgRBreast cancerERα coactivatorMammary glandHER4 intracellular domainProgesterone receptor expressionPositive breast carcinomaMalignant breast epitheliumPrimary breast tumorsMCF-7 variantEstrogen receptor coactivatorBreast tumor cell linesCell linesBreast tumor cellsTamoxifen responseMouse mammary glandProgesterone receptorReceptor expressionBreast carcinomaMCF-7 breast tumor cell linePatient responseBreast carcinogenesisEstrogen stimulationBreast epithelium
2009
GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer
Scott KL, Kabbarah O, Liang MC, Ivanova E, Anagnostou V, Wu J, Dhakal S, Wu M, Chen S, Feinberg T, Huang J, Saci A, Widlund HR, Fisher DE, Xiao Y, Rimm DL, Protopopov A, Wong KK, Chin L. GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer. Nature 2009, 459: 1085-1090. PMID: 19553991, PMCID: PMC2753613, DOI: 10.1038/nature08109.Peer-Reviewed Original ResearchConceptsTarget of rapamycinTrans-Golgi networkHuman cancersGenome-wide copy number analysisCopy number analysisRetromer complexGolgi proteinsHuman cancer cellsRapamycin sensitivityNew oncogeneGOLPH3Integrative analysisPotent oncogeneGenomic profilesBiochemical dataCancer cellsFunction studiesNumber analysisYeastSolid tumor typesCell sizeOncogeneMTORRapamycinMTOR inhibitorsGab2-Mediated Signaling Promotes Melanoma Metastasis
Horst B, Gruvberger-Saal SK, Hopkins BD, Bordone L, Yang Y, Chernoff KA, Uzoma I, Schwipper V, Liebau J, Nowak NJ, Brunner G, Owens D, Rimm DL, Parsons R, Celebi JT. Gab2-Mediated Signaling Promotes Melanoma Metastasis. American Journal Of Pathology 2009, 174: 1524-1533. PMID: 19342374, PMCID: PMC2671382, DOI: 10.2353/ajpath.2009.080543.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingBiomarkers, TumorBlotting, WesternCell MovementChromosomes, Artificial, BacterialComparative Genomic HybridizationFluorescent Antibody TechniqueGene DosageHumansIn Situ Hybridization, FluorescenceMelanomaNeoplasm InvasivenessNeoplasm MetastasisOligonucleotide Array Sequence AnalysisPolymorphism, Single NucleotideReverse Transcriptase Polymerase Chain ReactionSignal TransductionTissue Array AnalysisConceptsPI3K-Akt pathwayBacterial artificial chromosome array comparative genomic hybridizationInvasive potentialGrowth factor independenceSingle nucleotide polymorphism arrayCritical biological featuresHyperactivation of AKTMelanoma tumor progressionNucleotide polymorphism arrayTumor cell migrationArray comparative genomic hybridizationAdaptor proteinComparative genomic hybridizationRas-ERKFactor independenceMetastatic melanoma samplesMelanoma cell linesGab2Polymorphism arrayCopy numberCell migrationHuman cancersUndefined roleWide searchGenomic hybridizationActivated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model
Chien AJ, Moore EC, Lonsdorf AS, Kulikauskas RM, Rothberg BG, Berger AJ, Major MB, Hwang ST, Rimm DL, Moon RT. Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 1193-1198. PMID: 19144919, PMCID: PMC2626610, DOI: 10.1073/pnas.0811902106.Peer-Reviewed Original ResearchConceptsBeta-catenin signalingNormal melanocyte developmentTranscriptional profiling revealsWnt/beta-catenin signalingMelanoma cellsUp-regulates genesWnt/ß-cateninMelanoma progressionSmall molecule activatorsRole of WntMelanocyte developmentCell fateTranscriptional changesB16 murine melanoma cellsCellular differentiationProfiling revealsMelanocyte differentiationMelanoma cell linesMurine melanoma cellsß-cateninHuman melanoma cell linesWnt3aMurine melanoma modelCell linesReduced expressionAnalysis of Drosophila Segmentation Network Identifies a JNK Pathway Factor Overexpressed in Kidney Cancer
Liu J, Ghanim M, Xue L, Brown CD, Iossifov I, Angeletti C, Hua S, Nègre N, Ludwig M, Stricker T, Al-Ahmadie HA, Tretiakova M, Camp RL, Perera-Alberto M, Rimm DL, Xu T, Rzhetsky A, White KP. Analysis of Drosophila Segmentation Network Identifies a JNK Pathway Factor Overexpressed in Kidney Cancer. Science 2009, 323: 1218-1222. PMID: 19164706, PMCID: PMC2756524, DOI: 10.1126/science.1157669.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsApoptosisCarcinoma, Renal CellCell LineCompound Eye, ArthropodDrosophila melanogasterDrosophila ProteinsEmbryo, NonmammalianFushi Tarazu Transcription FactorsGene Expression ProfilingGene Regulatory NetworksHomeodomain ProteinsHumansJanus KinasesKidneyKidney NeoplasmsMolecular Sequence DataNervous SystemNuclear ProteinsPhosphoprotein PhosphatasesPhosphorylationRepressor ProteinsSignal TransductionTranscription FactorsTranscription, GeneticConceptsTranscription factorsClear cell renal cell carcinomaCell renal cell carcinomaKey transcription factorDrosophila segmentation networkConserved roleEmbryonic segmentationDrosophila melanogasterUbiquitin E3JNK signalingDependent apoptosisSPOPRenal cell carcinomaSPOP expressionKidney cancerTumor necrosis factorNew roleDrosophilaMelanogasterPuckeredGenesSignalingOverexpressedIdentificationApoptosis