Articleshttps://doi.org/10.1038/s41556-018-0083-61DepartmentofPathology,UniversityofCaliforniaSanDiego,LaJolla,CA,USA.2DepartmentofMolecularandCellularBiology,BeckmanResearchInstituteofCityofHope,Duarte,CA,USA.3DepartmentofCancerBiology,BeckmanResearchInstituteofCityofHope,Duarte,CA,USA.4SchoolofPharmacy,ChongqingMedicalUniversity,Chongqing,China.5DepartmentofPharmacologyandCancerBiology,DukeUniversity,Durham,NC,USA.6DepartmentofMolecularMedicine,BeckmanResearchInstituteofCityofHope,Duarte,CA,USA.7DepartmentofImmunologyandBiotherapy,TianjinMedicalUniversityCancerInstituteandHospital,Tianjin,China.8CityofHopeIrell&ManellaGraduateSchoolofBiologicalSciences,Duarte,CA,USA.9MooresCancerCenter,UniversityofCaliforniaSanDiego,LaJolla,CA,USA.*e-mail:emilywang@ucsd.eduCancerengagesadynamicinterplayamongcellsinthecancer-hostingniche1,2.Acrossthemanylevelsofintercellularcross-talk,aroleforcancer-secretedextracellularvesicles(EVs)hasbeenrecognized3,4.Throughtravellingintheinterstitialspacesandblood,EVstransferbiomoleculesbetweenadjacentordistantcells5–7.Cancer-derivedEVsareimplicatedintissueinvasion,angio-genesis,immuneevasionandmetastasis7–15,withmanyofthesefunctionsattributedtoEV-encapsulatedmicroRNA(miRNA)post-transcriptionallyregulatinggeneexpressioninnichecells16–18.Wepreviouslyreportedthatbreastcancer(BC)cellssecretemiR-105todestroytightjunctionsinvascularendothelialcellsandpromotemetastasis11,andthatBC-secretedmiR-122suppressesglucoseutilizationinapre-metastaticnichetooutsmartnutrientcompe-tition10.IncreasedlevelsofcirculatingmiR-105andmiR-122canbedetectedatapre-metastaticstageandcorrelatewiththeoccur-renceofmetastasisinBCpatients;systemicinterventionsofthesemiRNAssuppressBCmetastases10,11,19.Here,weextendourstudyofcancer-secretedmiRNAtothemetabolicreprogrammingofcancer-associatedfibroblasts(CAFs),amajorcellularcomponentoftumourstroma20.Proliferativecancercellsoftenacquireenhancedabilitiestoexploitnutrients,suchasglucoseandglutamine,tosupporttheirenergydemandandbiom...
