1NAMPTisaPotentOncogeneinColonCancerProgressionthatModulatesCancerStemCellPropertiesandresistancetotherapythroughSirt1andPARPAntonioLucena-Cacace1,2,DanielOtero-Albiol1,2,ManuelP.Jiménez-García1,2,SandraMuñoz-Galvan1,2andAmancioCarnero1,2,3(1)InstitutodeBiomedicinadeSevilla,IBIS,HospitalUniversitarioVirgendelRocio,UniversidaddeSevilla,ConsejoSuperiordeInvestigacionesCientificas,Sevilla,Spain.(2)CIBERONC,InstitutodeSaludCarlosIII,Madrid,Spain”(3)Correspondingauthor:AmancioCarneroInstitutodeBiomedicinadeSevilla/HUVR/CSICHospitalUniversitarioVirgendelRocioAvda.ManuelSiurots/n
41013,Sevilla,Spaine-mail:acarnero-ibis@us.esTelephone:(+34)955923111;Fax:(+34)955923101Keywords:NAMPT,Coloncancer,SIRT1,PARP1,CancerInitiatingCell,GeneSignature,Pluripotency,ClinicalOutcome.Runningtitle:NAMPTOverexpressionInducesCSCsinColonCancerConflictofInterest:Authorsdeclarenoconflictsofinterest.Research.onDecember6,2017.©2017AmericanAssociationforCancerclincancerres.aacrjournals.orgDownloadedfromAuthormanuscriptshavebeenpeerreviewedandacceptedforpublicationbuthavenotyetbeenedited.AuthorManuscriptPublishedOnlineFirstonDecember4,2017;DOI:10.1158/1078-0432.CCR-17-25752STATEMENTOFTRANSLATIONALRELEVANCEColorectalcancer(CRC)refractorydiseaseoftenreliesonnicotinamideadeninedinucleotide(NAD)-dependentmechanisms.HighlevelsofNADconfertherapyresistancetotumors.WereportthatNAMPT,therate-limitingenzymeofphysiologicalNADbiosynthesis,increasestumorigenicpropertiesandinducescancerstemcell-likepropertiesthroughpathwaysthatcontrolstemcellsignaling.NAMPTinhibitionincreasedthesensitivitytoapoptosisinbothNAMPT-expressingmaturecellsandcancer-initiatingcellpopulation.Therefore,NAMPTrepresentsanoveltherapeutictargetincoloncancerprogressionandrelapse,particularlytargetingtheCICsubsetofhumancoloncancers.WealsoreportanovelNAMPT-drivensignaturethatstratifyprognosisonCRCpatientsfromhightolowexpressiongroups.NAMPT-drivensignaturemayhelptostratifypatientsunabletorespondtoclassicalchemotherapytoenrollonNAMPTinhibi...
