pcadherin和结肠癌肝转移

pcadherin和结肠癌肝转移

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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

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