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1、TheAmericanJournalofPathology,Vol.179,No.1,July2011Copyright©2011AmericanSocietyforInvestigativePathology.PublishedbyElsevierInc.Allrightsreserved.DOI:10.1016/j.ajpath.2011.03.046TumorigenesisandNeoplasticProgressionP-CadherinPromotesLiverMetastasisand
2、Is
AssociatedwithPoorPrognosisinColonCancerLichaoSun,*HaiHu,*LiangPeng,*ZhuanZhou,*XuanZhao,*JianPan,*LixinSun,*ZhihuaYang,†andYuliangRan*FromtheStateKeyLaboratoryofMolecularOncology*andtheDepartmentofCellandMolecularBiology,†CancerInstitute(Hospital),
3、ChineseAcademyofMedicalSciences,PekingUnionMedicalCollege,Beijing,ChinaP-cadherinbelongstothefamilyofclassiccadherins,whichisimportantformaintainingcellularlocaliza-tionandtissueintegrity.Recently,ithasbecomeevi-dentthatP-cadherincontributestotheoncoge
4、nesisofmanytumortypes,includingmelanoma,prostate,breast,andcoloncarcinomas.Althoughcadherinswitchingisacrucialstepinmetastasis,theroleofP-cadherinincoloncancermetastasistotheliverisunknown.Inthisstudy,weperformedgeneexpres-sionanalysisandfoundthatthele
5、velofP-cadherinwashigherintissuefromlivermetastasesofcoloncancerthaninthecorrespondingprimarycoloncan-certissues.IHCanalysisalsoshowedthatP-cadherinexpressionwassignificantlyhigherinlivermetasta-sesthaninpairedprimarycolorectalcancertumors.KnockdownofP
6、-cadherinincoloncancercellsinhib-itedwoundhealing,proliferation,andcolonyforma-tionandresultedindevelopingfewerlivermetastaticfociandreducingthetumorburdeninvivo.Inhibi-tionofP-cadherinexpressionalsoinducedtheup-regulationofE-cadherinandthedown-regulat
7、ionof-cateninanditsdownstreamtargetmolecules,in-cludingsurvivinandc-Myc.Insummary,theseresultsuncoveranovelfunctionofP-cadherinintheregula-tionofcoloncancermetastasistotheliver,suggestingthatblockingtheactivityofP-cadherinoritsassociatedsignalingmaybe
8、avaluabletargetforthetreatmentofhepaticmetastasesofcoloncarcinomas.(AmJPathol2011,179:380–390;DOI:10.1016/j.ajpath.2011.03.046)Coloncancerisoneofthemostcommoncancersintheworldandhasahighpropensityforlivermetastasis.1,2Theprimarycauseofd
