CancerBiolMed2023.doi:10.20892/j.issn.2095-3941.2022.0750PERSPECTIVEIntercellulartransmissionofcGAS-STINGsignalingincancerQirouWu1,2,3,XiaohongLeng1,PinglongXu1,2,31MOELaboratoryofBiosystemsHomeostasisandProtectionandZhejiangProvincialKeyLaboratoryforCancerMolecularCellBiology,LifeSciencesInstitute,ZhejiangUniversity,Hangzhou310058,China;2InstituteofIntelligentMedicine,HangzhouGlobalScientificandTechnologicalInnovationCenter,ZhejiangUniversity(HIC-ZJU),Hangzhou310058,China;3CancerCenter,ZhejiangUniversity,Hangzhou310058,ChinaCellularcommunicationisnecessaryfororganizingmul-ticellularorganisms,andiscriticalintumorigenesisandprogression.ImmuneandtumorcellsusethecGAS-STINGmechanismtosenseandrespondtogenomicinstability,DNAdamage,andmitochondrialdysfunctioninducedbyextra-andintracellularstresses.Asanessentialcomponentofinnatenucleicacidsensing,cGAS-STINGsignalingiscriticalinvariouspathologicalprocesses,includingmicro-bialinfection,autoimmunity,inflammation,organdegen-eration,andmalignancy.ThecytosolicDNAsensorcyclicGMP-AMPsynthase(cGAS)sensesaberrantordisplaceddsDNAinthecytosolandsynthesizes2′3′-cyclicGMP-AMP(cGAMP).Endoplasmicreticulum(ER)-residentadaptorstimulatorofinterferongenes(STING),mobilizedbythissecondmessenger,istraffickedamongtheER,ER-Golgiintermediatecompartment,andGolgiapparatus,andformsdistinctSTINGsignalosomes,whichinturntriggervariousmolecularprogramscontrollingmRNAtransla-tion,autophagy,organellereorganization,andinterferon(IFN)production1.Thenon-canonicalfunctionsofcGAS-STINGsignalinghaverecentlygainedextensiveattention.Thesefunctionsoccurinvariouscellularprocesses,includ-ingsenescence,autophagy,andcap-dependentmRNAtranslation1,2.Notably,thecomplexityofcGAS-STINGsignalingisfur-therenhancedbyanintriguingfeatureofintercellulartrans-mission(Figure1)thathasrecentlybeenestablishedinseveralseminaldiscoveries.TheeffectiveintercellulartransferofcGAS-STINGsignalingenablesthesharingofcriticalinfor-mationarisingfrominfected,injured,orcancerouscellsandtheactiv...
