MetabolismShapestheTumorMicroenvironmentMiguelReina-Campos1,JorgeMoscat2,andMariaDiaz-Meco2,31SanfordBurnhamPrebysGraduateSchoolofBiomedicalSciences2CancerMetabolismandSignalingNetworksProgram,SanfordBurnhamPrebysMedicalDiscoveryInstitute,10901NorthTorreyPinesRoad,LaJolla,CA92037,USAAbstractTumorsarestronglyinfluencedbythesurroundingnormaltissue,whichformsaspecializednichetermedthetumormicroenvironment(TME).TheTMEismodeledbycancercellsfortheirownbenefitthroughacomplexarrayofinteractions.TheidentificationofnewformsofcommunicationwithintheTME,whicharedependentonthetumor’smetabolicactivity,hasexpandedourunderstandingofthisheterocellularregulationandhasrevealedpotentialtherapeutictargets.ThisreviewwillsummarizerecentfindingsonthemetabolicregulationoftumorcellsbytheTME.Theconceptstobediscussedincludetheexistenceofmetabolicintratumoralheterogeneity,thecontributionofcancerassociatedfibroblasts(CAFs)totumorprogression,andtheregulationoftumorimmunologybytumor-secretedmetabolites.GraphicalabstractIntroductionTumorcellshaveanextraordinarilyelevatedrequirementfornutrientstosustaintheirdemandinganabolicneedsandenergyproductionrates.Thus,extracellularnutrientsdictatetherateatwhichtumorcellsproliferate.However,unlikenormalcells,cancercellshavegreatermetabolicplasticity,whichallowsthemtobetteradapttolowerorchangingnutrientconditions[1]inwaysthatcan,inturn,reshapetheTME.3Correspondingauthor:mdmeco@sbpdiscovery.org.Publisher'sDisclaimer:ThisisaPDFfileofanuneditedmanuscriptthathasbeenacceptedforpublication.Asaservicetoourcustomersweareprovidingthisearlyversionofthemanuscript.Themanuscriptwillundergocopyediting,typesetting,andreviewoftheresultingproofbeforeitispublishedinitsfinalcitableform.Pleasenotethatduringtheproductionprocesserrorsmaybediscoveredwhichcouldaffectthecontent,andalllegaldisclaimersthatapplytothejournalpertain.HHSPublicAccessAuthormanuscriptCurrOpinCellBiol.Authormanuscript;availableinPMC2018October01.Publishedinfinaleditedformas:CurrOpinCellBiol.2017October;48:47...
