2022
Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer
Adua S, Arnal-Estapé A, Zhao M, Qi B, Liu Z, Kravitz C, Hulme H, Strittmatter N, López-Giráldez F, Chande S, Albert A, Melnick M, Hu B, Politi K, Chiang V, Colclough N, Goodwin R, Cross D, Smith P, Nguyen D. Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer. Nature Communications 2022, 13: 7690. PMID: 36509758, PMCID: PMC9744876, DOI: 10.1038/s41467-022-34889-z.Peer-Reviewed Original ResearchConceptsGene expression programsRas homolog family member ACancer cellsFamily member AEpidermal growth factor receptorExpression programsMetastatic cancer cellsSRF signalingGrowth factor receptorTumor microenvironmentLung cancerFunctional linkExtracellular lamininDrug-resistant cancer cellsMutant non-small cell lung cancerNon-small cell lung cancerCentral nervous system relapseMolecular studiesMember AEGFR-mutant lung cancerFactor receptorNervous system relapseCell lung cancerDisseminated tumor cellsBrain tumor microenvironmentHuman WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation
Cai WL, Chen JF, Chen H, Wingrove E, Kurley SJ, Chan LH, Zhang M, Arnal-Estape A, Zhao M, Balabaki A, Li W, Yu X, Krop ED, Dou Y, Liu Y, Jin J, Westbrook TF, Nguyen DX, Yan Q. Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation. ELife 2022, 11: e78163. PMID: 36043466, PMCID: PMC9584608, DOI: 10.7554/elife.78163.Peer-Reviewed Original ResearchConceptsBreast cancer cellsMetastatic breast cancerBreast cancerRibosomal gene expressionCancer cellsKnockdown of WDR5Vivo genetic screenReversible epigenetic mechanismsGenetic screenTranslation regulationTriple-negative breast cancerEpigenetic regulatorsEpigenetic mechanismsBreast cancer growthCancer-related deathTranslation efficiencyWDR5Novel therapeutic strategiesTranslation rateGene expressionCell growthAdvanced diseaseEffective therapyMetastatic capabilityPotent suppression
2021
Preclinical Models for the Study of Lung Cancer Pathogenesis and Therapy Development
Arnal-Estapé A, Foggetti G, Starrett JH, Nguyen DX, Politi K. Preclinical Models for the Study of Lung Cancer Pathogenesis and Therapy Development. Cold Spring Harbor Perspectives In Medicine 2021, 11: a037820. PMID: 34518338, PMCID: PMC8634791, DOI: 10.1101/cshperspect.a037820.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPatient-derived xenograftsPreclinical modelsLung cancer translational researchExperimental preclinical modelsLung cancer pathogenesisLung cancer cell linesNumerous preclinical modelsLung cancer subtypesLung cancer researchCancer translational researchCancer cell linesMouse modelNew therapeutic vulnerabilitiesCancer subtypesTumor progressionCancer pathogenesisTherapeutic vulnerabilitiesTranslational researchTherapy developmentCell linesCancer researchThree-dimensional culture systemCulture systemPathogenesisXenograftsTumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF
Cheok SK, Narayan A, Arnal-Estape A, Gettinger S, Goldberg SB, Kluger HM, Nguyen D, Patel A, Chiang V. Tumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF. JCO Precision Oncology 2021, 5: 163-172. PMID: 34250381, PMCID: PMC8232069, DOI: 10.1200/po.20.00292.Peer-Reviewed Original ResearchConceptsIntraparenchymal brain metastasesBrain metastasesCell-free DNAExtracranial tumorsBrain metastasis tissuesProgressive brain metastasesThird of patientsNormal pressure hydrocephalusTumor DNA mutationsPrimary cancer typeAnalysis of CSFSamples of CSFLeptomeningeal diseaseEffective surrogate markerBrain biopsyPressure hydrocephalusLumbar punctureSurrogate markerCancer-associated genesMetastasis tissuesPatientsMetastasisDiscordant responsesRenal cellsGenomic profiling
2020
Tumor progression and chromatin landscape of lung cancer are regulated by the lineage factor GATA6
Arnal-Estapé A, Cai WL, Albert AE, Zhao M, Stevens LE, López-Giráldez F, Patel KD, Tyagi S, Schmitt EM, Westbrook TF, Nguyen DX. Tumor progression and chromatin landscape of lung cancer are regulated by the lineage factor GATA6. Oncogene 2020, 39: 3726-3737. PMID: 32157212, PMCID: PMC7190573, DOI: 10.1038/s41388-020-1246-z.Peer-Reviewed Original ResearchConceptsChromatin landscapeTranscription factorsBone morphogenetic protein (BMP) signalingDiverse transcriptional programsAlters chromatin accessibilityMultiple genomic lociMorphogenetic protein signalingDistal enhancer elementsSelective transcription factorsEpithelial cell typesSurfactant protein CChromatin accessibilityGenomic lociTranscriptional programsLung adenocarcinoma progressionTumor progressionEpigenetic mechanismsProtein signalingBiological functionsLUAD progressionLUAD cellsEnhancer elementsLineage dependencyTumor suppressionLung cancer cellsSpecific chromatin landscapes and transcription factors couple breast cancer subtype with metastatic relapse to lung or brain
Cai WL, Greer CB, Chen JF, Arnal-Estapé A, Cao J, Yan Q, Nguyen DX. Specific chromatin landscapes and transcription factors couple breast cancer subtype with metastatic relapse to lung or brain. BMC Medical Genomics 2020, 13: 33. PMID: 32143622, PMCID: PMC7060551, DOI: 10.1186/s12920-020-0695-0.Peer-Reviewed Original ResearchConceptsOpen chromatin signaturesTranscription factorsChromatin landscapeChromosome conformation captureOpen chromatin landscapeSpecific chromatin landscapesHomophilic cell adhesionTransposase-accessible chromatinEnhancer-promoter interactionsSpecific transcription factorsActive chromatin sitesATAC-seq dataMetastatic cellsGene expression dataChromatin signaturesConformation captureChromatin sitesActive chromatinATAC-seqEpigenomic propertiesChIP-seqChromatin immunoprecipitationEndothelial cell migrationEpigenomic analysisTranscriptomic differences
2019
Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis
Wingrove E, Liu ZZ, Patel KD, Arnal-Estapé A, Cai WL, Melnick MA, Politi K, Monteiro C, Zhu L, Valiente M, Kluger HM, Chiang VL, Nguyen DX. Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis. Cell Reports 2019, 27: 1277-1292.e7. PMID: 31018140, PMCID: PMC6592283, DOI: 10.1016/j.celrep.2019.03.085.Peer-Reviewed Original ResearchConceptsBrain metastasesBrain tumor microenvironmentLineage programTumor microenvironmentTumor plasticityStromal gene expressionTranscriptomic hallmarksGene expressionTranscriptional hallmarksMultiple tumor typesMolecular landscapeStromal interactionsMajor siteIntact tissueNeuroinflammatory responseSyngeneic modelPatient biopsiesTumor typesMetastasisMalignant cellsDifferent subtypesTumor cellsHallmarkTranscriptomeCells
2017
Adrenergic nerves activate an angio-metabolic switch in prostate cancer
Zahalka AH, Arnal-Estapé A, Maryanovich M, Nakahara F, Cruz CD, Finley LWS, Frenette PS. Adrenergic nerves activate an angio-metabolic switch in prostate cancer. Science 2017, 358: 321-326. PMID: 29051371, PMCID: PMC5783182, DOI: 10.1126/science.aah5072.Peer-Reviewed Original ResearchMeSH KeywordsAlkyl and Aryl TransferasesAnimalsCarrier ProteinsElectron Transport Complex IVEndothelium, VascularGene DeletionHumansMaleMembrane ProteinsMiceMitochondrial ProteinsNeovascularization, PathologicNerve FibersNorepinephrineOxidative PhosphorylationProstateProstatic NeoplasmsReceptors, Adrenergic, beta-2Signal TransductionTumor MicroenvironmentExtracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases
Stevens LE, Cheung WKC, Adua SJ, Arnal-Estapé A, Zhao M, Liu Z, Brewer K, Herbst RS, Nguyen DX. Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases. Cancer Research 2017, 77: 1905-1917. PMID: 28196904, PMCID: PMC5468792, DOI: 10.1158/0008-5472.can-16-1978.Peer-Reviewed Original ResearchConceptsBrain metastatic nicheRisk of relapseDistant metastasisPoor prognosisLUAD subtypesLung tumorsLung adenocarcinomaLUAD cellsMetastatic outgrowthMetastatic nicheCancer ResCancer cellsECM-mediated signalingExtracellular matrix moleculesCell survivalMolecular signaturesDifferential expressionHMMRMatrix moleculesImportant mechanismCellsRelapseAdenocarcinomaPrognosisMetastasis
2015
Sweets for a Bitter End: Lung Cancer Cell–Surface Protein Glycosylation Mediates Metastatic Colonization
Arnal-Estapé A, Nguyen DX. Sweets for a Bitter End: Lung Cancer Cell–Surface Protein Glycosylation Mediates Metastatic Colonization. Cancer Discovery 2015, 5: 109-111. PMID: 25656895, PMCID: PMC4340588, DOI: 10.1158/2159-8290.cd-15-0013.Peer-Reviewed Original Research