REVIEWARTICLEOPENExosome-mediatedmetabolicreprogramming:theemergingroleintumormicroenvironmentremodelinganditsinfluenceoncancerprogressionEnliYang1,2,XuanWang1,2,ZhiyuanGong1,2,MiaoYu1,2,HaiweiWu1,2andDongshengZhang1,2Metabolicreprogrammingisreportedtobeoneofthehallmarksofcancer,whichisanadaptivemechanismbywhichfast-growingcancercellsadapttotheirincreasingenergydemands.Recently,extracellularvesicles(EVs)knownasexosomeshavebeenrecognizedascrucialsignalingmediatorsinregulatingthetumormicroenvironment(TME).Meanwhile,theTMEisahighlyheterogeneousecosystemincorporatingcancercells,fibroblasts,adipocytes,endothelialcells,mesenchymalstemcells,andextracellularmatrix.Accumulatedevidenceindicatesthatexosomesmaytransferbiologicallyfunctionalmoleculestotherecipientcells,whichfacilitatecancerprogression,angiogenesis,metastasis,drugresistance,andimmunosuppressionbyreprogrammingthemetabolismofcancercellsandtheirsurroundingstromalcells.Inthisreview,wepresenttheroleofexosomesintheTMEandtheunderlyingmechanismofhowexosomesexacerbatetumordevelopmentthroughmetabolicreprogramming.Inaddition,wewillalsodiscussthepotentialroleofexosomestargetingmetabolicprocessasbiomarkersfortumordiagnosisandprognosis,andexosomes-mediatedmetabolicreprogrammingaspotentialtargetsforcancertherapy.Furthermore,abetterunderstandingofthelinkbetweenexosomesandmetabolicreprogramming,andtheirimpactoncancerprogression,wouldprovidenovelinsightsforcancerpreventionandtreatmentinthefuture.SignalTransductionandTargetedTherapy(2020)5:242;https://doi.org/10.1038/s41392-020-00359-5INTRODUCTIONInthepastdecade,thecancermetabolismhasreceivedenormousinterestandwideattention.Acommonmetabolicfeatureofcancercellsisobtainingnecessarynutrientfromanutrient-deficientenvironmentandusingthenutrienttomaintaincellviability,proliferation,andbuildbiomass.Themetabolicactivityofcancercellsisalteredcomparedwithnormalcells,andthesechangessupporttheacquisitionandpreservationofmalignantfeatures.Therefore,metabolicreprogrammingisregardedasoneoftheh...
