NFS1undergoespositiveselectioninlungtumoursandprotectscellsfromferroptosisSamanthaW.Alvarez1,2,*,VladislavO.Sviderskiy1,2,*,ErdemM.Terzi1,2,ThalesPapagiannakopoulos1,2,AndreL.Moreira1,2,SylviaAdams1,2,DavidM.Sabatini3,4,5,6,7,KıvançBirsoy3,4,5,6,7,8,†,andRichardPossemato1,2,3,4,5,6,7,†1DepartmentofPathology,NewYorkUniversitySchoolofMedicine,NewYork,NewYork10016,USA.2Laura&IsaacPerlmutterCancerCenter,NewYorkUniversitySchoolofMedicine,NewYork,NewYork10016,USA.3WhiteheadInstituteforBiomedicalResearch,NineCambridgeCenter,Cambridge,Massachusetts02142,USA.4HowardHughesMedicalInstitute,DepartmentofBiology,MassachusettsInstituteofTechnology,Cambridge,Massachusetts02139,USA.5TheDavidH.KochInstituteforIntegrativeCancerResearch,77MassachusettsAvenue,Cambridge,Massachusetts02139,USA.6DepartmentofBiology,MassachusettsInstituteofTechnology,Cambridge,Massachusetts02139,USA.7BroadInstituteofHarvardandMassachusettsInstituteofTechnology,SevenCambridgeCenter,Cambridge,Massachusetts02142,USA.8LaboratoryofMetabolicRegulationandGenetics,TheRockefellerUniversity,1230YorkAvenue,NewYork10065,USA.AbstractEnvironmentalnutrientlevelsimpactcancercellmetabolism,resultingincontext-dependentgeneessentiality1,2.Here,usingloss-of-functionscreeningbasedonRNAinterference,weshowthatenvironmentaloxygenlevelsareamajordriverofdifferentialessentialitybetweeninvitromodelReprintsandpermissionsinformationisavailableatwww.nature.com/reprints.CorrespondenceandrequestsformaterialsshouldbeaddressedtoR.P.(richard.possemato@nyumc.org),K.B.(kbirsoy@rockefeller.edu)orD.M.S.(sabatini@wi.mit.edu).*Theseauthorscontributedequallytothiswork.†Presentaddresses:LaboratoryofMetabolicRegulationandGenetics,TheRockefellerUniversity,1230YorkAvenue,NewYork,NewYork10065,USA(K.B.);DepartmentofPathology,NewYorkUniversitySchoolofMedicine,NewYork,NewYork10016,USA(R.P.).SupplementaryInformationisavailableintheonlineversionofthepaper.AuthorContributionsR.P.,K.B.,andD.M.Sconceivedtheprojectanddesignedtheexperiments.R.P.andK.B.perf...