Targeting Hypoxia-Inducible Factor-1α/Pyruvate Dehydrogenase Kinase 1 Axis by Dichloroacetate Suppresses Bleomycin-induced Pulmonary Fibrosis
Goodwin J, Choi H, Hsieh MH, Neugent ML, Ahn JM, Hayenga HN, Singh PK, Shackelford DB, Lee IK, Shulaev V, Dhar S, Takeda N, Kim JW. Targeting Hypoxia-Inducible Factor-1α/Pyruvate Dehydrogenase Kinase 1 Axis by Dichloroacetate Suppresses Bleomycin-induced Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2017, 58: 216-231. PMID: 28915065, PMCID: PMC5805994, DOI: 10.1165/rcmb.2016-0186oc.Peer-Reviewed Original ResearchConceptsPyruvate dehydrogenase kinase 1Myofibroblast differentiationPulmonary fibrosisFibrotic progressionHIF-1αGlycolytic metabolismDehydrogenase kinase 1Knockout mouse modelHypoxia-inducible factorMetabolic reprogrammingCellular metabolismPotential therapeutic strategyKinase 1Glycolytic switchGenomic deletionsSustained activationMicroenvironmental influencesPreclinical efficacyGlycolytic reprogrammingPharmacological inhibitionReprogrammingMouse modelDifferentiationPharmacological approachesTherapeutic strategiesThe distinct metabolic phenotype of lung squamous cell carcinoma defines selective vulnerability to glycolytic inhibition
Goodwin J, Neugent ML, Lee SY, Choe JH, Choi H, Jenkins DMR, Ruthenborg RJ, Robinson MW, Jeong JY, Wake M, Abe H, Takeda N, Endo H, Inoue M, Xuan Z, Yoo H, Chen M, Ahn JM, Minna JD, Helke KL, Singh PK, Shackelford DB, Kim JW. The distinct metabolic phenotype of lung squamous cell carcinoma defines selective vulnerability to glycolytic inhibition. Nature Communications 2017, 8: 15503. PMID: 28548087, PMCID: PMC5458561, DOI: 10.1038/ncomms15503.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAdultAgedAged, 80 and overAnimalsCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCell Line, TumorCohort StudiesDeoxyglucoseFemaleFluorodeoxyglucose F18Gene Expression ProfilingGene Expression Regulation, NeoplasticGlucoseGlucose Transporter Type 1GlycolysisHumansHydroxybenzoatesLungLung NeoplasmsMaleMiceMice, NudeMiddle AgedPhenotypePositron-Emission TomographyPrognosisSurvival AnalysisUp-RegulationXenograft Model Antitumor AssaysConceptsNon-small cell lung cancerSquamous cell carcinomaLung SqCCCell carcinomaNSCLC subtypesGlycolytic inhibitionLung squamous cell carcinomaCell lung cancerPatient-derived xenograftsNSCLC tumor samplesNSCLC cell linesCancer Genome AtlasClinical presentationPoor prognosisTherapeutic optionsLung cancerPredominant subtypeDistinct metabolic phenotypesSelective vulnerabilityLung adenocarcinomaMurine modelTherapeutic strategiesSqCCTumor samplesMetabolic signatures