2015
Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling
York AG, Williams KJ, Argus JP, Zhou QD, Brar G, Vergnes L, Gray EE, Zhen A, Wu NC, Yamada DH, Cunningham CR, Tarling EJ, Wilks MQ, Casero D, Gray DH, Yu AK, Wang ES, Brooks DG, Sun R, Kitchen SG, Wu TT, Reue K, Stetson DB, Bensinger SJ. Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling. Cell 2015, 163: 1716-1729. PMID: 26686653, PMCID: PMC4783382, DOI: 10.1016/j.cell.2015.11.045.Peer-Reviewed Original ResearchConceptsImport of cholesterolI interferonType I IFNsSTING-dependent mannerCholesterol biosynthetic pathwayI IFNsCombination of biosynthesisBiosynthetic fluxBiosynthetic pathwayLong-chain fatty acidsIsotope tracer analysisMetabolic shiftMetabolic pathwaysType I interferonCholesterol biosynthesisLipid requirementsChain fatty acidsInnate immunityBiosynthesisFatty acidsPool sizePathwayMechanistic studiesViral challengeFree cholesterol
2013
An Essential Requirement for the SCAP/SREBP Signaling Axis to Protect Cancer Cells from Lipotoxicity
Williams K, Argus J, Zhu Y, Wilks M, Marbois B, York A, Kidani Y, Pourzia A, Akhavan D, Lisiero D, Komisopoulou E, Henkin A, Soto H, Chamberlain B, Vergnes L, Jung M, Torres J, Liau L, Christofk H, Prins R, Mischel P, Reue K, Graeber T, Bensinger S. An Essential Requirement for the SCAP/SREBP Signaling Axis to Protect Cancer Cells from Lipotoxicity. Cancer Research 2013, 73: 2850-2862. PMID: 23440422, PMCID: PMC3919498, DOI: 10.1158/0008-5472.can-13-0382-t.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CycleCell Line, TumorCell ProliferationFatty Acid SynthasesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceMice, Inbred NODModels, StatisticalNeoplasm TransplantationNeoplasmsSignal TransductionStearoyl-CoA DesaturaseSterolsConceptsSterol regulatory element-binding proteinsFatty acid synthesisSREBP activityCellular growthFatty acid poolKey transcriptional regulatorCancer cellsFatty acid desaturationAcid synthesisAcid poolElement-binding proteinMetabolic flux analysisTranscriptional regulatorsLipid biosynthesisNovel mechanistic explanationStearoyl-CoA desaturase-1Fatty acid synthase activityCancer metabolismCancer cell growthSignaling AxisCell growthFlux analysisSynthase activityDesaturase 1Lipid profiling