Thebadseedgardener:Deubiquitinasesinthecancerstem-cellsignalingnetworkandtherapeuticresistanceGuan-ZhongQiub,WeiSunc,Ming-ZhuJind,JingLine,Pei-GangLub,⁎,Wei-LinJina,f,⁎⁎aInstituteofNanoBiomedicineandEngineering,DepartmentofInstrumentScienceandEngineering,KeyLab.forThinFilmandMicrofabricationTechnologyofMinistryofEducation,SchoolofElectronicInformationandElectronicEngineering,ShanghaiJiaoTongUniversity,Shanghai200240,PRChinabDepartmentofNeurosurgery,GeneralHospitalofJinanMilitaryCommand,Jinan250031,PRChinacDepartmentofNeurosurgery,ChangzhengHospital,SecondMilitaryMedicalUniversity,Shanghai200003,PRChinadShanghaiJiaoTongUniversitySchoolofMedicine,Shanghai200025,PRChinaeDepartmentofNeurosurgery,GeneralHospitalofWesternAirForce,Chengdu610061,PRChinafNationalCentersforTranslationalMedicine,ShanghaiJiaoTongUniversity,Shanghai200240,PRChinaabstractarticleinfoAvailableonline3December2016Tumorsarecomprisedofhighlyheterogeneouspopulationsofcells,ofwhichonlyasmallsubsetofstem-likecellspossesstheabilitytoregeneratetumorsinvivo.Theserarecancerstemcells(CSCs)havebeenregardedasthe“badseeds”accountedfortumorinitiation,progression,metastasis,relapseandtherapeuticresistance.CSC-targetedtherapyseemstobeabetteravenueforradicalcureofcancer.Deubiquitinases(DUBs),specificallydisassemblingubiquitinchains,havebeendemonstratedtoplayanimportantroleinrigidlymaintainingthebal-ancebetweenubiquitinationanddeubiquitinationforproteinqualitycontrolandhomeostasisinnormalcircum-stances.DysfunctionorderegulationofDUBsalwaysleadstoaseriesofdisorders,evenmalignanttransformation.DespitetheaccumulativeevidencethatDUBinhibitorsincancerremedymainlytargetthetumorbulk,sideeffectsliketoxicityandresistancearestillhardnutstocrack.Inthisarticle,wereviewthecon-ceptofubiquitinproteasomesystem(UPS)andhallmarksofCSCsrelatedtotumorobstinacy.Weprimarilysum-marizetheCSC-relatedfactorsandsignalingpathwaysandfocusonthefunctionofDUBsonbiologicaltraitsofCSCs.Wealsoillustratetheopportunitiesandchallengesfortheapplicat...
