MicroenvironmentalautophagypromotestumourgrowthNadjaS.Katheder1,2,RojyarKhezri1,2,*,FergalO’Farrell1,2,*,SebastianW.Schultz1,2,AshishJain1,2,3,MohammedM.Rahman1,2,KayO.Schink1,2,TheodossisA.Theodossiou4,TerjeJohansen3,GáborJuhász5,6,DavidBilder7,AndreasBrech1,2,HaraldStenmark1,2,andTorErikRusten1,21DepartmentofMolecularCellBiology,InstituteforCancerResearch,OsloUniversityHospital,Montebello,N-0379Oslo,Norway2CentreforCancerBiomedicine,FacultyofMedicine,UniversityofOslo,Montebello,N-0379Oslo,Norway3MolecularCancerResearchGroup,InstituteofMedicalBiology,UiT-TheArcticUniversityofNorway,9037Tromsø,Norway4DepartmentofRadiationBiology,InstituteforCancerResearch,OsloUniversityHospital,Montebello,N-0379Oslo,Norway5InstituteofGenetics,BiologicalResearchCentre,HungarianAcademyofSciences,Szeged,H-6726Hungary6DepartmentofAnatomy,CellandDevelopmentalBiology,EötvösLorándUniversity,BudapestH-1117,Hungary7DepartmentofMolecularandCellBiology,UniversityofCalifornia,Berkeley,Berkeley,California94720-3200,USAAbstractAsmalignanttumoursdevelop,theyinteractintimatelywiththeirmicroenvironmentandcanactivateautophagy1,acatabolicprocesswhichprovidesnutrientsduringstarvation.Howtumoursregulateautophagyinvivoandwhetherautophagyaffectstumourgrowthiscontroversial2.Herewedemonstrate,usingawellcharacterizedDrosophilamelanogastermalignanttumourmodel3,4,thatnon-cell-autonomousautophagyisinducedbothinthetumourmicroenvironmentandsystemicallyindistanttissues.TumourgrowthcanbepharmacologicallyrestrainedusingReprintsandpermissionsinformationisavailableatwww.nature.com/reprints.CorrespondenceandrequestsformaterialsshouldbeaddressedtoT.E.R.(tor.erik.rusten@rr-research.no).*Theseauthorscontributedequallytothiswork.SupplementaryInformationisavailableintheonlineversionofthepaper.AuthorContributionsN.S.K.,H.S.,D.B.,T.J.andT.E.R.designedtheresearch;N.S.K.,R.K.,F.O.F,A.J.,S.W.S.,M.M.R.,K.O.S.,T.A.T.andT.E.R.,performedexperimentsandanalysedthedata;G.J.developedtransgenicautophagyreporteranimals;andN.S.K....
