2019
p63 and SOX2 Dictate Glucose Reliance and Metabolic Vulnerabilities in Squamous Cell Carcinomas
Hsieh MH, Choe JH, Gadhvi J, Kim YJ, Arguez MA, Palmer M, Gerold H, Nowak C, Do H, Mazambani S, Knighton JK, Cha M, Goodwin J, Kang MK, Jeong JY, Lee SY, Faubert B, Xuan Z, Abel ED, Scafoglio C, Shackelford DB, Minna JD, Singh PK, Shulaev V, Bleris L, Hoyt K, Kim J, Inoue M, DeBerardinis RJ, Kim TH, Kim JW. p63 and SOX2 Dictate Glucose Reliance and Metabolic Vulnerabilities in Squamous Cell Carcinomas. Cell Reports 2019, 28: 1860-1878.e9. PMID: 31412252, PMCID: PMC7048935, DOI: 10.1016/j.celrep.2019.07.027.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsApoptosisCarcinoma, Squamous CellCell ProliferationFemaleGene Expression Regulation, NeoplasticGlucoseGlucose Transporter Type 1HumansMaleMembrane ProteinsMiceMice, Inbred NODMice, KnockoutMice, SCIDPhosphatidylinositol 3-KinasesProtein Serine-Threonine KinasesSignal TransductionSOXB1 Transcription FactorsTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsSquamous cell carcinomaCell carcinomaInsufficient therapeutic optionsBlood insulin levelsRenal glucose reabsorptionBlood glucose concentrationTumor growth inhibitionAnti-oxidative capacityMultiple anatomical sitesPI3K/AktGlucose restrictionSCC patientsWorse survivalKetogenic dietInsulin levelsTherapeutic optionsCancer mortalityGlucose reabsorptionSCC tumorsBlood glucoseSCC cellsAnatomical sitesCancer typesMetabolic vulnerabilitiesOxidative stress
2017
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 strategies