Cathepsin G, a Neutrophil Protease, Induces Compact Cell-Cell Adhesion in MCF-7 Human Breast Cancer Cells英文文献资料.docVIP

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Cathepsin G, a Neutrophil Protease, Induces Compact Cell-Cell Adhesion in MCF-7 Human Breast Cancer Cells英文文献资料.doc

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Cathepsin G, a Neutrophil Protease, Induces Compact Cell-Cell Adhesion in MCF-7 Human Breast Cancer Cells英文文献资料

HindawiPublishingCorporation MediatorsofIn?ammation Volume2009,ArticleID850940,11pages doi:10.1155/2009/850940 ResearchArticle CathepsinG,aNeutrophilProtease,InducesCompactCell-Cell AdhesioninMCF-7HumanBreastCancerCells TomoyaKudo, 1 HideakiKigoshi, TakashiHagiwara, TakahisaTakino, 1 1 2 andSatoruYui 1 MasatoshiYamazaki, 1 1 2 FacultyofPharmaceuticalSciences,TeikyoUniversity,1091-1Sagamiko,Sagamihara,Kanagawa229-0195,Japan DepartmentofMolecularVirologyandOncology,CancerResearchInstitute,KanazawaUniversity, 13-1Takara-machi,Kanazawa920-0934,Japan CorrespondenceshouldbeaddressedtoSatoruYui,sat-yui@pharm.teikyo-u.ac.jp Received23May2009;Revised6August2009;Accepted21August2009 RecommendedbyHiddeBult CathepsinGisaserineproteasesecretedbyactivatedneutrophilsthatplayaroleinthein?ammatoryresponse.Becauseneutrophils areknowntobeinvadingleukocytesinvarioustumors,theirproductsmayin?uencethecharacteristicsoftumorcellssuchas thegrowthstate,motility,andtheadhesivenessbetweencellsortheextracellularmatrix.Here,wedemonstratethatcathepsin G induces cell-cell adhesion of MCF-7 human breast cancer cells resulting from the contact inhibition of cell movement on ?bronectinbutnotontypeIVcollagen.CathepsinGsubsequentlyinducedcellcondensation,averycompactcellcolony,resulting duetotheincreasedstrengthofE-cadherin-mediatedcell-celladhesion.CathepsinGactionisproteaseactivity-dependentand wasinhibitedbythepresenceofserineproteaseinhibitors.CathepsinGpromotesE-cadherin/catenincomplexformationand Rap1activationinMCF-7cells,whichreportedlyregulatesE-cadherin-basedcell-celljunctions.CathepsinGalsopromotesE- cadherin/protein kinase D1 (PKD1) complex formation, and Go6976, the selective PKD1 inhibitor, suppressed the cathepsin G-inducedcellcondensation.Our?ndingsprovidethe?rstevidencethatcathepsinGregulatesE-cadherinfunction,suggesting thatcathepsinGhasanovelmodulatoryroleagainsttumorcell-celladhesion. Copyright?2009TomoyaKudoetal.Thisisanopenaccessarticledistribut