2024
Targeting TREX1 induces innate immune response in drug-resistant Small Cell Lung Cancer.
Murayama T, Mahadevan NR, Meador CB, Ivanova EV, Pan Y, Knelson EH, Tani T, Nakayama J, Ma X, Thai TC, Hung YP, Kim W, Watanabe H, Cai K, Hata AN, Paweletz CP, Barbie DA, Canadas I. Targeting TREX1 induces innate immune response in drug-resistant Small Cell Lung Cancer. Cancer Res Commun 2024 PMID: 39177280, DOI: 10.1158/2767-9764.CRC-24-0360.Peer-Reviewed Original ResearchTargeting DHX9 triggers tumor-intrinsic interferon response and replication stress in Small Cell Lung Cancer
Murayama T, Nakayama J, Jiang X, Miyata K, Morris A, Cai K, Prasad R, Ma X, Efimov A, Belani N, Gerstein E, Tan Y, Zhou Y, Kim W, Maruyama R, Campbell K, Chen L, Yang Y, Balachandran S, Canadas I. Targeting DHX9 triggers tumor-intrinsic interferon response and replication stress in Small Cell Lung Cancer. Cancer Discovery 2024, 14: 468-491. PMID: 38189443, PMCID: PMC10905673, DOI: 10.1158/2159-8290.cd-23-0486.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerDExD/H-box helicase 9Cell lung cancerCold tumorsLung cancerResponse to immune-checkpoint blockadeInnate immunityEnhance immunotherapy efficacyImmune-checkpoint blockadeImmunogenic tumor microenvironmentImmunologically cold tumorsNucleic acid-sensing pathwaysActivate innate immunityAntitumor immunityImmunotherapy efficacyReplication stressTumor microenvironmentTumor growthViral mimicryTumorImmune responseCancer cellsInterferon responseCytoplasmic dsRNACancer
2023
Activation of KrasG12D in Subset of Alveolar Type II Cells Enhances Cellular Plasticity in Lung Adenocarcinoma
Chaudhary P, Xu X, Wang G, Hoj J, Rampersad R, Asselin-Labat M, Ting S, Kim W, Tamayo P, Pendergast A, Onaitis M. Activation of KrasG12D in Subset of Alveolar Type II Cells Enhances Cellular Plasticity in Lung Adenocarcinoma. Cancer Research Communications 2023, 3: 2400-2411. PMID: 37882674, PMCID: PMC10668634, DOI: 10.1158/2767-9764.crc-22-0408.Peer-Reviewed Original ResearchConceptsType II cellsLung adenocarcinomaDual-positive cellsII cellsKRAS-mutant lung adenocarcinomaDevelopment of novel targeted therapeuticsTumor-initiating cellsNotch signalingAlveolar type II cellsNovel targeted therapeuticsCell of originThree-dimensional organoid culturesSOX2 upregulationKRAS activationAdenocarcinomaMouse modelTherapeutic strategiesProliferation of cellsGain-of-functionRNA sequencing analysisTransplantation studiesCellular plasticityOrganoid culturesSOX2 levelsNotch pathwayDeciphering the Functional Roles of Individual Cancer Alleles Across Comprehensive Cancer Genomic Studies.
Ma JY, Ting S, Tam B, Pham T, Reich M, Mesirov J, Tamayo P, Kim W. Deciphering the Functional Roles of Individual Cancer Alleles Across Comprehensive Cancer Genomic Studies. BioRxiv 2023 PMID: 38014215, DOI: 10.1101/2023.11.14.567106.Publications for non-academic audiencesTargeting the RET tyrosine kinase in neuroblastoma: A review and application of a novel selective drug design strategy
Steen E, Basilaia M, Kim W, Getz T, Gustafson J, Zage P. Targeting the RET tyrosine kinase in neuroblastoma: A review and application of a novel selective drug design strategy. Biochemical Pharmacology 2023, 216: 115751. PMID: 37595672, PMCID: PMC10911250, DOI: 10.1016/j.bcp.2023.115751.Peer-Reviewed Original ResearchConceptsRET inhibitorsRET inhibitionSolid tumorsIncreased RET expressionAssociated with poor prognosisPediatric solid tumorsNeuroblastoma tumor cellsPapillary thyroid cancerTyrosine kinaseOncogenic RET mutationsRET tyrosine kinaseProgression of multiple typesTransmembrane receptor tyrosine kinaseRET mutationsRET expressionReceptor tyrosine kinasesThyroid cancerNeuroblastoma tumorsPoor prognosisPreclinical studiesTumor cellsBreast cancerKinase inhibitorsLung adenocarcinomaClinical trialsTargeting TBK1 to overcome resistance to cancer immunotherapy
Sun Y, Revach O, Anderson S, Kessler E, Wolfe C, Jenney A, Mills C, Robitschek E, Davis T, Kim S, Fu A, Ma X, Gwee J, Tiwari P, Du P, Sindurakar P, Tian J, Mehta A, Schneider A, Yizhak K, Sade-Feldman M, LaSalle T, Sharova T, Xie H, Liu S, Michaud W, Saad-Beretta R, Yates K, Iracheta-Vellve A, Spetz J, Qin X, Sarosiek K, Zhang G, Kim J, Su M, Cicerchia A, Rasmussen M, Klempner S, Juric D, Pai S, Miller D, Giobbie-Hurder A, Chen J, Pelka K, Frederick D, Stinson S, Ivanova E, Aref A, Paweletz C, Barbie D, Sen D, Fisher D, Corcoran R, Hacohen N, Sorger P, Flaherty K, Boland G, Manguso R, Jenkins R. Targeting TBK1 to overcome resistance to cancer immunotherapy. Nature 2023, 615: 158-167. PMID: 36634707, PMCID: PMC10171827, DOI: 10.1038/s41586-023-05704-6.Peer-Reviewed Original ResearchConceptsOvercome resistance to cancer immunotherapyResistance to cancer immunotherapyPD-1 blockadeCancer immunotherapyImmune-evasion genesResponse to PD-1 blockadePatient-derived tumor modelsPatient-derived organoidsEffective treatment strategiesTBK1 inhibitionPD-1Effector cytokinesConcordant findingsTumor cellsTumor modelCaspase-dependent cell deathResponse to TNFTreatment strategiesTargeting TBK1ImmunotherapyPharmacological toolsBlockadeTumor spheroidsCell deathTBK1
2022
MET-induced CD73 restrains STING-mediated immunogenicity of EGFR-mutant lung cancer
Yoshida R, Saigi M, Tani T, Springer B, Shibata H, Kitajima S, Mahadevan N, Campisi M, Kim W, Kobayashi Y, Thai T, Haratani K, Yamamoto Y, Sundararaman S, Knelson E, Vajdi A, Canadas I, Uppaluri R, Paweletz C, Miret J, Lizotte P, Gokhale P, Jänne P, Barbie D. MET-induced CD73 restrains STING-mediated immunogenicity of EGFR-mutant lung cancer. Cancer Research 2022, 82: 4079-4092. PMID: 36066413, PMCID: PMC9627131, DOI: 10.1158/0008-5472.can-22-0770.Peer-Reviewed Original ResearchConceptsEGFR-mutant lung cancerEGFR-TKI-resistant cellsThird-generation EGFR tyrosine kinase inhibitorMET-amplifiedT cell responsesPemetrexed treatmentLung cancerCD8+ T cell immunogenicityEGFR-TKI treatment failureEGFR tyrosine kinase inhibitorsInhibit T cell responsesUpregulation of CD73Humanized mouse modelTyrosine kinase inhibitorsT-cell immunogenicityCell line studiesMET amplificationEGFR-TKIsTKI resistanceTreatment failureCancer immunogenicityCD73 inhibitionT cellsPemetrexedEnhanced immunogenicityCHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity
Bernareggi D, Xie Q, Prager B, Yun J, Cruz L, Pham T, Kim W, Lee X, Coffey M, Zalfa C, Azmoon P, Zhu H, Tamayo P, Rich J, Kaufman D. CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity. Nature Communications 2022, 13: 1899. PMID: 35393416, PMCID: PMC8990014, DOI: 10.1038/s41467-022-29469-0.Peer-Reviewed Original ResearchConceptsResistance to NK cell-mediated cytotoxicityHead and neck squamous cell carcinomaNK cell-mediated killingNK cell-mediated cytotoxicityCell-mediated cytotoxicityCell-mediated killingTumor cellsGlioblastoma stem cellsNatural killerNK cellsIncreased NK cell-mediated killingMechanism of tumor immune escapeHead and neck squamous cell carcinoma modelResistance to NK cellsNeck squamous cell carcinomaApoptosis of NK cellsNK cell-mediated immunotherapyExtracellular vesiclesCell-mediated immunotherapyTumor immune escapeImmunodeficient mouse modelSquamous cell carcinomaNK cell migrationIncreased chemokine secretionHuman glioblastoma stem cells
2021
An expanded universe of cancer targets
Hahn W, Bader J, Braun T, Califano A, Clemons P, Druker B, Ewald A, Fu H, Jagu S, Kemp C, Kim W, Kuo C, McManus M, B. Mills G, Mo X, Sahni N, Schreiber S, Talamas J, Tamayo P, Tyner J, Wagner B, Weiss W, Gerhard D, Dancik V, Gill S, Hua B, Sharifnia T, Viswanathan V, Zou Y, Dela Cruz F, Kung A, Stockwell B, Boehm J, Dempster J, Manguso R, Vazquez F, Cooper L, Du Y, Ivanov A, Lonial S, Moreno C, Niu Q, Owonikoko T, Ramalingam S, Reyna M, Zhou W, Grandori C, Shmulevich I, Swisher E, Cai J, Chan I, Dunworth M, Ge Y, Georgess D, Grasset E, Henriet E, Knútsdóttir H, Lerner M, Padmanaban V, Perrone M, Suhail Y, Tsehay Y, Warrier M, Morrow Q, Nechiporuk T, Long N, Saultz J, Kaempf A, Minnier J, Tognon C, Kurtz S, Agarwal A, Brown J, Watanabe-Smith K, Vu T, Jacob T, Yan Y, Robinson B, Lind E, Kosaka Y, Demir E, Estabrook J, Grzadkowski M, Nikolova O, Chen K, Deneen B, Liang H, Bassik M, Bhattacharya A, Brennan K, Curtis C, Gevaert O, Ji H, Karlsson K, Karagyozova K, Lo Y, Liu K, Nakano M, Sathe A, Smith A, Spees K, Wong W, Yuki K, Hangauer M, Kaufman D, Balmain A, Bollam S, Chen W, Fan Q, Kersten K, Krummel M, Li Y, Menard M, Nasholm N, Schmidt C, Serwas N, Yoda H, Ashworth A, Bandyopadhyay S, Bivona T, Eades G, Oberlin S, Tay N, Wang Y, Weissman J. An expanded universe of cancer targets. Cell 2021, 184: 1142-1155. PMID: 33667368, PMCID: PMC8066437, DOI: 10.1016/j.cell.2021.02.020.Peer-Reviewed Original ResearchConceptsNon-oncogene dependenciesDiversity of therapeutic targetsSomatically altered genesCancer targetCancer allelesInfluence therapyCancer genomesGenomic characterizationTherapeutic strategiesAltered genesCancer featuresCancer genesClinical translationCancerCancer biologyTherapeutic targetTumorGenomeGenes
2020
WNT Signaling Driven by R-spondin 1 and LGR6 in High-grade Serous Ovarian Cancer
LEE S, JUN J, KIM W, TAMAYO P, HOWELL S. WNT Signaling Driven by R-spondin 1 and LGR6 in High-grade Serous Ovarian Cancer. Anticancer Research 2020, 40: 6017-6028. PMID: 33109540, PMCID: PMC9312105, DOI: 10.21873/anticanres.14623.Peer-Reviewed Original ResearchConceptsHigh-grade serous ovarian cancerGene set enrichment analysisSerous ovarian cancerWnt signalingOvarian surfaceExpression of RSPO1Gene set enrichment analysis methodRNA-seq dataControl cell fateR-spondinOvarian cancerAnalysis of genesNormal tissuesWnt signaling pathwayHuman Protein AtlasAdjacent genesImpact overall survivalLevel of expressionRNA-seqAssociation studiesCell fateCopy numberGO pathwaysAnalysis of TCGAEnrichment analysisMesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers
Stern J, Hibshman G, Hu K, Ferrara S, Costello J, Kim W, Tamayo P, Cech T, Huang F. Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers. Molecular Cancer Research 2020, 18: 1050-1062. PMID: 32276990, PMCID: PMC8020009, DOI: 10.1158/1541-7786.mcr-19-1244.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorChromatin ImmunoprecipitationEpithelial-Mesenchymal TransitionExtracellular Signal-Regulated MAP KinasesGene Expression ProfilingGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansMutationNeoplasmsPromoter Regions, GeneticSequence Analysis, RNASmall Molecule LibrariesTelomeraseTumor MicroenvironmentConceptsCell linesAnalysis of cell linesAdherens junction protein E-cadherinKnock-down experimentsExpression signaturesRAS pathway inhibitorsInhibition of MEK1Promoter mutationsSensitivity to specific drugsCatalytic subunit of telomeraseJunction protein E-cadherinProtein E-cadherinSubunit of telomeraseInvestigational treatment approachesMesenchymal transcription factorsPan-cancer analysisCatalytic subunitEpithelial-to-mesenchymal transitionTranscription factorsCell line growthMutantsPathway effectorsTERT mRNA expressionMAPK signalingProliferative immortalityCannabinoids Promote Progression of HPV-Positive Head and Neck Squamous Cell Carcinoma via p38 MAPK Activation
Liu C, Sadat S, Ebisumoto K, Sakai A, Panuganti B, Ren S, Goto Y, Haft S, Fukusumi T, Ando M, Saito Y, Guo T, Tamayo P, Yeerna H, Kim W, Hubbard J, Sharabi A, Gutkind J, Califano J. Cannabinoids Promote Progression of HPV-Positive Head and Neck Squamous Cell Carcinoma via p38 MAPK Activation. Clinical Cancer Research 2020, 26: 2693-2703. PMID: 31932491, PMCID: PMC7538010, DOI: 10.1158/1078-0432.ccr-18-3301.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCannabinoidsCell MovementCell ProliferationFemaleHead and Neck NeoplasmsHumansMiceMice, NudeP38 Mitogen-Activated Protein KinasesPapillomaviridaePapillomavirus InfectionsPrognosisReceptors, CannabinoidSquamous Cell Carcinoma of Head and NeckTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsHead and neck squamous cell carcinomaHPV-positive head and neck squamous cell carcinomaHPV-positive HNSCC cell linesNeck squamous cell carcinomaHNSCC cell linesSingle-sample gene set enrichment analysisSquamous cell carcinomaP38 MAPK pathway activationHNSCC cohortCell carcinomaMAPK pathway activationHPV-negative head and neck squamous cell carcinomaHuman papillomavirus (HPV)-related headCell linesAnimal modelsCannabinoid receptor activationHPV- HNSCC patientsHead and neck squamous cell carcinomas dataMarijuana usePathway activationDaily marijuana useWhole-genome expression analysisCannabinoid exposureHNSCC patientsP38 MAPK activationGαs (GNAS) suppression of the p53 genomic‐stability checkpoint unleashes RAS‐driven oncogenesis
Steffen D, Tiriac H, Valera J, Amornphimoltham P, Kim W, Taylor S, Hunter T, Tamayo P, Gutkind J. Gαs (GNAS) suppression of the p53 genomic‐stability checkpoint unleashes RAS‐driven oncogenesis. The FASEB Journal 2020, 34: 1-1. DOI: 10.1096/fasebj.2020.34.s1.04604.Peer-Reviewed Original ResearchTrp53 tumor suppressor geneCooperation of rasMDM2-mediated p53 ubiquitinationHuman intestinal organoid modelP53 E3 ubiquitin ligaseSquamous cell carcinomaIn vitro ubiquitination assayP53 protein accumulationChemical carcinogen DMBASkin of adult miceTumor suppressor genePhosphorylation of Mdm2Control genome stabilityE3 ubiquitin ligaseRAS mutant tumorsRas-driven oncogenesisCarcinogenesis in vivoSubstrate of PKAConstitutively activating mutationAppendix cancerPan-cancer analysisActivation of signalingPatient sequencing dataBenign tumorsCell carcinomaSTRIPAK directs PP2A activity toward MAP4K4 to promote oncogenic transformation of human cells
Kim J, Berrios C, Kim M, Schade A, Adelmant G, Yeerna H, Damato E, Iniguez A, Florens L, Washburn M, Stegmaier K, Gray N, Tamayo P, Gjoerup O, Marto J, DeCaprio J, Hahn W. STRIPAK directs PP2A activity toward MAP4K4 to promote oncogenic transformation of human cells. ELife 2020, 9: e53003. PMID: 31913126, PMCID: PMC6984821, DOI: 10.7554/elife.53003.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCalmodulin-Binding ProteinsCell ProliferationCell Transformation, NeoplasticFemaleGene Knockdown TechniquesHEK293 CellsHeterograftsHumansIntracellular Signaling Peptides and ProteinsMicePhosphoprotein PhosphatasesProtein Serine-Threonine KinasesSignal TransductionTranscription FactorsYAP-Signaling ProteinsConceptsStriatin-interacting phosphatase and kinaseSV40 small t antigenB subunitCell transformationPP2A subunitsHippo pathway effector YAP1Regulatory B subunitPP2A B subunitsPP2A-mediated dephosphorylationSmall t antigenInduce cell transformationPP2A functionPP2A complexPP2A activityOncogenic transformationSubunit interactionsPP2AHuman cancersT antigenMAP4K4SubunitAssociated with STCell alterationsPartial lossCells
2019
The multikinase inhibitor RXDX-105 is effective against neuroblastoma in vitro and in vivo
Flynn S, Lesperance J, Macias A, Phanhthilath N, Paul M, Kim J, Tamayo P, Zage P. The multikinase inhibitor RXDX-105 is effective against neuroblastoma in vitro and in vivo. Oncotarget 2019, 10: 6323-6333. PMID: 31695841, PMCID: PMC6824878, DOI: 10.18632/oncotarget.27259.Peer-Reviewed Original ResearchRXDX-105Small molecule inhibitor of multiple kinasesPediatric cancer-related deathsExtracranial solid tumor of childhoodSolid tumor of childhoodHigh riskHigh-risk neuroblastomaInhibitor of multiple kinasesTumor of childhoodNeuroblastoma in vitroExtracranial solid tumorTreatment of neuroblastoma cellsCancer-related deathsNeuroblastoma cellsRelapsed neuroblastomaRelapsed tumorsMaintenance therapyCell cycle arrestXenograft tumorsTumor growthSmall molecule inhibitorsRas-MAPK pathwayCombined inhibitionRET phosphorylationTumorCyclin E Overexpression in Human Mammary Epithelial Cells Promotes Epithelial Cancer-Specific Copy Number Alterations
Giraldez S, Tamayo P, Wineinger N, Kim W, Reed S. Cyclin E Overexpression in Human Mammary Epithelial Cells Promotes Epithelial Cancer-Specific Copy Number Alterations. IScience 2019, 19: 850-859. PMID: 31513970, PMCID: PMC6739637, DOI: 10.1016/j.isci.2019.08.043.Peer-Reviewed Original ResearchChromosomal copy number alterationsCopy number alterationsCyclin ECell cycle regulatory proteinsOverexpression of cyclin EChromosomal lociCyclin E overexpressionEpithelial cell clonesRegulatory proteinsReplication stressCell cycleAberrant mitosesS phaseEpithelial-like tumorsCyclinE overexpressionCell clonesClonesOncogenesisComputational approachReplicationPotential mechanismsChromosomal damageCellsLociModelling bistable tumour population dynamics to design effective treatment strategies
Akhmetzhanov A, Kim J, Sullivan R, Beckman R, Tamayo P, Yeang C. Modelling bistable tumour population dynamics to design effective treatment strategies. Journal Of Theoretical Biology 2019, 474: 88-102. PMID: 31077681, PMCID: PMC9534689, DOI: 10.1016/j.jtbi.2019.05.005.Peer-Reviewed Original ResearchConceptsDrug resistanceHeterogeneous tumorsTumor cellsTreatment strategiesDevelopment of optimal therapeutic strategiesEffects of targeted drugsBRAF-mutant melanomaProcess of tumor growthOptimal therapeutic strategyDrug resistance characteristicsHeterogeneous tumor cellsReverse drug resistanceActivated alternative pathwayEmergence of resistanceCancer treatment modalityEffective treatment strategiesDesigning effective treatment strategiesDrug holidayBRAF inhibitorsPeriodate treatmentDrug regimensTreatment modalitiesGenetic alterationsTumor growthDrug sensitivity
2018
Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS
Kitajima S, Asahina H, Chen T, Guo S, Quiceno L, Cavanaugh J, Merlino A, Tange S, Terai H, Kim J, Wang X, Zhou S, Xu M, Wang S, Zhu Z, Thai T, Takahashi C, Wang Y, Neve R, Stinson S, Tamayo P, Watanabe H, Kirschmeier P, Wong K, Barbie D. Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS. Cancer Cell 2018, 34: 439-452.e6. PMID: 30205046, PMCID: PMC6422029, DOI: 10.1016/j.ccell.2018.08.009.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsAntineoplastic Agents, ImmunologicalCarcinoma, Non-Small-Cell LungCell Line, TumorDisease Models, AnimalDrug Resistance, NeoplasmHEK293 CellsHumansImmunity, InnateInsulin-Like Growth Factor ILung NeoplasmsMiceMice, TransgenicMitogen-Activated Protein Kinase KinasesPhosphoproteinsProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene Proteins p21(ras)Transcription FactorsYAP-Signaling ProteinsConceptsGenetically engineered mouse modelsMediators of acquired resistanceDownstream of KRASBET inhibitor JQ1Effective therapeutic strategyTumor shrinkageTargeted therapyIntermittent treatmentYAP1 signalingMouse modelPathway inhibitionBET inhibitionTherapeutic strategiesInhibitor JQ1YAP1 upregulationOncogenic KRASBET inhibitorsOvercome resistancePromoter acetylationIntrinsic resistancePotential translationKRASMEKInnateInhibitionAn alternative splicing switch in FLNB promotes the mesenchymal cell state in human breast cancer
Li J, Choi P, Chaffer C, Labella K, Hwang J, Giacomelli A, Kim J, Ilic N, Doench J, Ly S, Dai C, Hagel K, Hong A, Gjoerup O, Goel S, Ge J, Root D, Zhao J, Brooks A, Weinberg R, Hahn W. An alternative splicing switch in FLNB promotes the mesenchymal cell state in human breast cancer. ELife 2018, 7: e37184. PMID: 30059005, PMCID: PMC6103745, DOI: 10.7554/elife.37184.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsBase SequenceBreast NeoplasmsCell Line, TumorEpithelial-Mesenchymal TransitionExonsFemaleFilaminsGene Expression Regulation, NeoplasticGenome, HumanHumansHyaluronan ReceptorsMesenchymal Stem CellsMice, NudeNeoplasm ProteinsOpen Reading FramesProtein IsoformsReproducibility of ResultsRNA, MessengerRNA-Binding ProteinsConceptsEpithelial-to-mesenchymal transitionAlternative splicing of mRNA precursorsMesenchymal cell stateSplicing of mRNA precursorsCell statesRNA-binding proteinsAlternative splicing switchDysregulation of splicingBreast cancer patient samplesEMT gene signatureRegulation of epithelial-to-mesenchymal transitionCancer patient samplesInduce epithelial-to-mesenchymal transitionFOXC1 transcription factorRNA-seqAlternative splicingExpression screeningMRNA precursorsRegulating tumor cell plasticityRegulatory stepTranscription factorsSplicing switchProtein productionDiverse functionsIncreased tumorigenicityTumor innate immunity primed by specific interferon-stimulated endogenous retroviruses
Cañadas I, Thummalapalli R, Kim J, Kitajima S, Jenkins R, Christensen C, Campisi M, Kuang Y, Zhang Y, Gjini E, Zhang G, Tian T, Sen D, Miao D, Imamura Y, Thai T, Piel B, Terai H, Aref A, Hagan T, Koyama S, Watanabe M, Baba H, Adeni A, Lydon C, Tamayo P, Wei Z, Herlyn M, Barbie T, Uppaluri R, Sholl L, Sicinska E, Sands J, Rodig S, Wong K, Paweletz C, Watanabe H, Barbie D. Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses. Nature Medicine 2018, 24: 1143-1150. PMID: 30038220, PMCID: PMC6082722, DOI: 10.1038/s41591-018-0116-5.Peer-Reviewed Original ResearchConceptsInnate immune signalingSmall cell lung cancerEndogenous retrovirusesCell lung cancerPro-tumorigenic cytokinesImmune signalingAnalysis of cell linesCancer immunotherapyMesenchymal cell stateIFN-gTumor subpopulationsLung cancerLong terminal repeatHuman tumorsSPARC expressionMesenchymal markersTumorBi-directional transcriptionChromatin-modifying enzymesSTAT1 signalingCell linesCancerInnate immunityInducible SPARCS expressionGene promoter