Epithelial-mesenchymaltransition(EMT)isanessentialprocessduringdevelopmentwherebyepithelialcellsaquiremesenchymal,fibroblast-likepropertiesanddisplayreducedintracellularadhesionandincreasedmotility.Thisisacriticalfeatureofnormalembryonicdevelopment,whichisalsoutilizedbymalignantepithelialtumorstospreadbeyondtheirorigin.Thistightlyregulatedprocessisassociatedwithanumberofcellularandmolecularevents.EMTdependsonareductioninexpressionofcelladhesionmolecules.Cadherinsmediatecalcium-dependentcell-celladhesionandplaycriticalrolesinnormaltissuedevelopment.E-cadherinisconsideredanactivesuppressorofinvasionandgrowthofmanyepithelialcancers.Recentstudiesindicatethatcancercellshaveup-regulatedN-cadherininadditiontolossofE-cadherin.Thischangeincadherinexpressioniscalledthe"cadherinswitch"anddownregulationofE-cadherinisoneofthehallmarksofEMT.Tightjunctions,orzonulaoccludens,formacontinuousbarriertofluidsacrosstheepitheliumandendothelium.TheyfunctioninregulationofparacellularpermeABIlityandinthemaintenanceofcellpolarity,blockingthemovementoftransmembraneproteinsbetweentheapicalandthebasolateralcellsurfaces.Tightjunctionsarecomposedofclaudinandoccludinproteins,whichjointhejunctionstotheCytoskeleton.ZonaoccludensproteinsZO-1,2,and3(alsoknownasTJP1,2,and3)areperipheralmembraneadaptorproteinsthatlinkjunctionaltransmembraneproteinssuchasoccludinandclaudintotheactincytoskeleton.ZO-1and-2arerequiredfortightjunctionformationandfunction;mutationsinZO-1andClaudininduceEMT.Vimentinisanintermediatefilamentofmesenchymaloriginandispresentatearlydevelopmentalstages.Vimentin'sdynamicstructuralchangesandspatialre-organizationinresponsetoextracellularstimulihelpstocoordinatevarioussignalingpathways.beta-cateninisakeydownstreameffectorintheWntsignalingpathway.ItisimplicatedintwomajorBIOLOGicalprocessesinvertebrates:earlyembryonicdevelopmentandtumOrigenesis.beta-cateninalsoactivatesSlug.Slug(SNAI2)isawidelyexpressedtranscriptionalrepressorandmemberoftheSnailfamilyofzincfingertranscriptionfactors.SimilartotherelatedSnailprotein,SlugbindstotheE-cadherinpromoterregiontorepresstranscriptionduringdevelopment.ThebindingofSlugtointegrinpromotersequencesrepressesintegrinexpressionandresultsinreducedcelladhesion.DownregulationofE-cadherinexpressionoccursduringtheEMTduringembryonicdevelopment.ZEBfamilyproteinsarezincfingerandhomeoboxdomaincontainingtranscriptionfactors.OneofthetargetssuppressedbyZEBproteinsisE-cadherin.

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