Galectin-3 Facilitates Cell Motility in Gastric Cancer by Up-Regulating Protease-Activated Receptor-1(PAR-1) and Matrix Metalloproteinase-1(MMP-1) 英文参考文献.docVIP

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Galectin-3 Facilitates Cell Motility in Gastric Cancer by Up-Regulating Protease-Activated Receptor-1(PAR-1) and Matrix Metalloproteinase-1(MMP-1) 英文参考文献.doc

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Galectin-3 Facilitates Cell Motility in Gastric Cancer by Up-Regulating Protease-Activated Receptor-1(PAR-1) and Matrix Metalloproteinase-1(MMP-1) 英文参考文献

Galectin-3FacilitatesCellMotilityinGastricCancerby Up-RegulatingProtease-ActivatedReceptor-1(PAR-1) andMatrixMetalloproteinase-1(MMP-1) Seok-JunKim1,3,Ji-YoungShin1,Kang-DuckLee1,Young-KiBae2,Il-JuChoi1,SeokHeePark3 ,Kyung- HeeChun1* 1GastricCancerBranch,DivisionofTranslationalandClinicalResearchI,NationalCancerCenterResearchInstituteandHospital,Jungbalsan-ro,Ilsandong-gu,Goyang-si, Gyeonggi-do, Republic of Korea, 2Cancer Experimental RecoursesBranch, Division ofCancer Biology, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, RepublicofKorea,3DepartmentofBiologicalScience,SungkyunkwanUniversity,Jangan-gu,Suwon-si,Gyeonggi-do,RepublicofKorea Abstract Background:Galectin-3isknowntoregulatecancermetastasis.However,theunderlyingmechanismhasnotbeendefined. ThroughtheDNAmicroarraystudiesaftergalectin-3silencing,wedemonstratedherethatgalectin-3playsakeyroleinup- regulatingtheexpressionsofprotease-activatedreceptor-1(PAR-1)andmatrixmetalloproteinase-1(MMP-1)PAR-1thereby promotinggastriccancermetastasis. Methodology/Principal Findings: We examined the expression levels of Galectin-3, PAR-1, and MMP-1 in gastric cancer patient tissues and also the effects of silencing these proteins with specific siRNAs and of over-expressing them using specificlenti-viralconstructs.Wealsoemployedzebrafishembryomodelforanalysisofinvivogastriccancercellinvasion. Thesestudiesdemonstratedthat:a)galectin-3silencingdecreasestheexpressionofPAR-1.b)galectin-3over-expression increases cell migration and invasion and this increase can be reversed by PAR-1 silencing, indicating that galectin-3 increasescellmigrationandinvasionviaPAR-1up-regulation.c)galectin-3directlyinteractswithAP-1transcriptionalfactor, andthiscomplexbindstoPAR-1promoteranddrivesPAR-1transcription.d)galectin-3alsoamplifiesphospho-paxillin,a PAR-1downstreamtarget,byincreasingMMP-1expression.MMP-1silencingblocksphospho-paxillinamplificationandcell invasioncausedbygalectin-3over-expression.e)Silencingofeithergalectin-3,P