Cellulartransformationisaccompaniedbymanycellularchanges,includinguncontrolledproliferation,lossofthedifferentiatedcellmorphology,andinvasionoftheextracellularmatrix.Degradationoftheextracellularmatrixisakeycomponentoftumorcellinvasionintosurroundingtissues.Matrixmetalloproteinases(MMPs)areaclassofproteasessecretedbytumorcells,degrADIngtheproteinsoftheextracellularmatrixandallowingmetastasis.DruginhibitorsofMMPsareonestrategytocontrolcancerandblockmetastasis.Insearchingforgenesthatreversetheroundedmorphologyoftransformedcellsinculture,RECKwasidentified(reversion-inducing,cysteine-richproteinwithKazalmotifs).RECKisamembrane-anchoredinhibitorofmatrixmetalloproteinases,inhibitingMMP-2,MMP-9andMT1-MMP.TheprocessingofMMPstotheiractiveformoccursattheplasmamembrane,makingthelocalizationofRECKatthemembraneakeytoitspotentactivityasaninhibitorofMMPactivity.SolublesecretedMMPinhibitorshavealsobeenidentified,TIMPs,whichappeartobelessactiveatinhibitingMMPsandevenperhapstobeessentialforMMPmaturation.TheinhibitionofMMPsbyRECKinhibitsinvasionoftissues,metastasisandtumorangiogenesis,andisessentialfornormaldevelopment.Inadditiontoplayingaroleintissueinvasionincancer,theactivityofMMPsinangiogenesis,inflammation,anddevelopmentisregulatedbyinhibitorssuchasRECKandTIMPs.RECKexpressionisinhibitedbyras,suggestingonecomponentbywhichrasinducestransformation.HighlevelsofRECKexpressionintumorsiscorrelatedwithcancerpatientsurvivalandoverexpressionofRECKmayofferatherapeuticstrategyforthecontrolofcancer.

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