dMyc Functions Downstream of Yorkie to Promote the Supercompetitive Behavior of Hippo Pathway Mutant Cells 英文参考文献.docVIP

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dMyc Functions Downstream of Yorkie to Promote the Supercompetitive Behavior of Hippo Pathway Mutant Cells 英文参考文献.doc

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dMyc Functions Downstream of Yorkie to Promote the Supercompetitive Behavior of Hippo Pathway Mutant Cells 英文参考文献

dMycFunctionsDownstreamofYorkietoPromotethe SupercompetitiveBehaviorofHippoPathwayMutant Cells MarcelloZiosi1.,LuisAlbertoBaena-Lo′pez2.,DanielaGrifoni1,3*,FrancescaFroldi1,AndreaPession4, FlavioGaroia5,VincenzoTrotta3,PaolaBellosta6,SandroCavicchi3,AnnalisaPession1 1DipartimentodiPatologiaSperimentale,AlmaMaterStudiorum,Bologna,Italy,2NationalInstituteforMedicalResearch,London,UnitedKingdom,3Dipartimentodi BiologiaEvoluzionisticaSperimentale,AlmaMaterStudiorum,Bologna,Italy,4DipartimentodiGinecologia,OstetriciaePediatria,AlmaMaterStudiorum,Bologna,Italy, 5NGBGeneticss.r.l,UniversityofFerrara,Ferrara,Italy,6DepartmentofBiology,CityCollegeoftheCityUniversityofNewYork,NewYork,NewYork,UnitedStatesof America Abstract GeneticanalysesinDrosophilaepitheliahavesuggestedthatthephenomenonof‘‘cellcompetition’’couldparticipatein organ homeostasis. It has been speculated that competition between different cell populations within a growing organ might play a role as either tumor promoter or tumor suppressor, depending on the cellular context. The evolutionarily conservedHippo(Hpo)signalingpathwayregulatesorgansizeandpreventshyperplasticdiseasefromfliestohumansby restrictingtheactivityofthetranscriptionalcofactorYorkie(yki).RecentdataindicatealsothatmutationsinseveralHpo pathwaymembersprovidecellswithacompetitiveadvantagebyunknownmechanisms.Hereweprovideinsightintothe mechanism by which the Hpo pathway is linked to cell competition, by identifying dMyc as a target gene of the Hpo pathway, transcriptionally upregulated by the activity of Yki with different binding partners. We show that the cell- autonomousupregulationofdMycisrequiredforthesupercompetitivebehaviorofYki-expressingcellsandHpopathway mutantcells,whereastherelativelevelsofdMycbetweenHpopathwaymutantcellsandwild-typeneighboringcellsare criticalfordeterminingwhethercellcompetitionpromotesatumor-suppressingortumor-inducingbehavior.Alltogether, these data provide a paradigmatic example of cooperation between tumor suppre