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1、CancerCellArticleOrai1andSTIM1AreCriticalforBreastTumorCellMigrationandMetastasisShengyuYang,1J.JillianZhang,1andXin-YunHuang1,*1DepartmentofPhysiology,WeillMedicalCollegeofCornellUniversity,NewYork,NY10065,USA*Correspondence:xyhuang@med.cornell.eduDOI10.1016/j.ccr.2008.12.
2、019SUMMARYTumormetastasisistheprimarycauseofdeathofcancerpatients.Understandingthemolecularmechanismsunderlyingtumormetastasiswillprovidepotentialdrugtargets.WereportherethatOrai1andSTIM1,bothofwhichareinvolvedinstore-operatedcalciumentry,areessentialforbreasttumorcellmigra
3、tioninvitroandtumormetastasisinmice.ReductionofOrai1orSTIM1byRNAinterferenceinhighlymetastatichumanbreastcancercellsortreatmentwithapharmacologicalinhibitorofstore-operatedcalciumchannelsdecreasedtumormetastasisinanimalmodels.OurdatademonstratearoleforOrai1andSTIM1intumorme
4、tastasisandsuggeststore-operatedcalciumentrychannelsaspotentialcancertherapeutictargets.INTRODUCTIONtumorcellsintolymphaticandbloodvesselsaswellastheextravasationoftumorcellsintothesecondaryorgans(MareelDespitethesignificantimprovementinbothdiagnosticandandLeroy,2003;Steeg,2
5、006).Cellmigrationisasequentialtherapeuticmodalitiesforthetreatmentofcancerpatients,andinterrelatedmultistepprocessinvolvingtheformationofmetastasisstillrepresentsthemajorcauseofmortality,beinglamellipodia/membraneprotrusionsatthefrontedge,cyclesofresponsiblefor90%ofallcan
6、cerdeaths(Christofori,2006;Ha-adhesionanddetachment,cellbodycontraction,andtailretrac-nahanandWeinberg,2000).Metastasisisthemultistepprocesstion(Ridleyetal.,2003).Focaladhesionturnoverplaysapivotalwhereinaprimarytumorspreadsfromitsinitialsitetosecondaryroleincellmigration.S
7、mall,nascentfocaladhesionsatthetissues/organs(Fidler,2003;Weiss,2000).Todisseminatefromleadingedgeserveastractionpointsfortheforcesthatmoveprimarytumorsandestablishsecondarytumors,cancercellsthecellbodyforward.Ontheotherhand,disassemblyoffocalmustsucceedinmigration/invasion
8、,infiltrationintocirculation,adhesionsattherearallowstheretractionoftherearandnetsu
