Rac1与肿瘤的研究进展

315201110http//．gjbl．netInternationalJournalofPathologyandClinicalMedicineVol．31No．5Oct．20112011－09－042011－09－29。[e-mail][e-mail]310006292008SK301009K07409A077。ThisworkwassupportedbyNationalNaturalScienceFoundationofChina31000629theFoun-dationofScienceandTechnologyProgramofHunanProvince2008SK3010InnovationPlatformOpenFundsforUniversityinHu-nanProvincial09K074andtheKeyProjectofScientificResearchFoundationofDepartmentofEducationHunanProvinceP．R．China09A077．Rac11121．2．421001Rho、、、、。RasC31Rho、、。Rac1doi10．3969/j．issn．1673-2588．2011．10．009AdvancesinresearchonRac1andtumorZHANGShuo1JIANGHao1SUQi21．DepartmentofMedicalOncologyFirstAffiliatedHospital2．CancerResearchInstituteUniversityofSouthChinaHengyangHunan421001ChinaAbstractThefamilyofRhoasmolecularswitchplaysavitalroleinmultiplecellfunctionssuchascellmotilityactionreorganizationtumormalignanttransformationinvasionmetastasisangio-genesisandregulationoftranscriptionfactor．Ras-relatedC3botulinumtoxinsubstrate1Rac1amemberofRhofamilyhasanimportantroleincellapoptosisproliferationmotilityinvasionmetasta-sisandangiogenesis．KeywordsRac1cellapoptosiscellproliferationcellmotilityinvasionmetasta-sisangiogenesisRacRac1Rac2Rac3Rac1Rac1b。Rac1。Rac1、。1Rac1Rac129kb77p22。Rac11．2kb2．5kb2。Rac1RhoguanosinetriphosphataseGTPaseguanosinediphosphateGDPguanosinetriphosphateGTPGDPGTP。Rac1。GDP/GTP30145Rac1311guaninenucle-otideexchangefactorsGEFs。GTPGDPGTPaseGTP。2GTPaseactivatingpro-teinsCAPs。GTPaseGTPGTPase。3guaninenucleotidedissociationinhibitorsGDIs。GDPGTPaseGDP。Rac、1。、、、、、、Rac1。Rac1bRac1Rac1。Rac1C-、、Rac1。Rac1、。Rac1bRhoRac1。Rac1bRac1Rac12。Rac1Rho。Rac1bRac1Rho、、。2Rac1。。、、。、、。Rac13、。vas-cularendothelialgrowthfactorVEGF、4。VEGF2SrcRacVav2Rac1Rac1nucleotide-freemutantG15ARac1Rac15。alphavbeta3Rac16。Eph、。EphEphrins。Ephrins-A1Vav2Vav3EphA2Rac17。EphA2Ephrin-A1Rac18。Ephrin-A1-3phosphatidylinositol3-kinasesPI3KRac18。。9AGS、SGC7901、HepG2rac1mRNARac1-1αVEGF、phosphataseandtensinhomologPTEN、53tumorprotein53p53。Rac1。Ma10Rac1RacCAVEGF1/2、、2TekRacCAN-。survivinsurvivinEx3Rac111。urokinase-typeplasminogenactivatorreceptoruPAR、B。Malla12uPARBJAK/STAT2Rac1gp91phoxD14Rb。3Rac1、Rac1。Rac1Rac11145http//．gjbl．net31。B2B-celllymphoma2Bcl-2Rac1Bcl-2Rac1Bcl-213。Du14K-rasRac1N17Rac。Bosco15NF2Wnt。Rac14WntNF2。4Rac13D5、。IL-8PI3K-Rac116。RacScar/WaveArp2/317。Rac1p53insulinreceptortyrosinekinasesubstratep53IRSp53NRac1RCBIRSp53IRSp53SH3WAVE2-Abi1Rac1-IRSp53-WAVE2-Abi1Arp2/3118。5Rac1、、、、。5．1Rac1Limk1LimLimkinaseLimkactin-depolymerizingfactorADF/Cofilin。、LimkRho-Rho/P21-LIMK-/-LIMK-/19。RhoGTPaseLimk1Limk2508505Limk1Limk220。LimkCofilin3Cofilin21。Rac/Cdc42Pak1Lim20RhoAROCKLim22。Delorme23Rac1Pak1ROCKLimk1Cofilin。Bagheri-Yarmand24Rac1Cdc42Limk1urokinase-typeplasminogenactivatoruPAuPAuPAuPAuPA。5．2Rac1--epithelialmesenchymaltransi-tionEMT。EMT。EMT、。EMT。Rac1。βtransforminggrowthfactorbetaTGF-βEMTEMTSmadSmad。Tobar25TGF-beta1Rac1-NOXs-ROSκBnuclearfactor-kappabetaNF-κBuPA9matrixmetalloproteinase9MMP-9EMT。Rac1-3/RasC31/c-junN-EMT26。Bakin27Rac1N17TGF-βp382EMT。。2145Rac131EMT。Stallings-Mann28Rac1bEMTRac1breactiveoxygenspeciesROSROSSnailEMT。Radisky29MMP-3EMT。EMTuPAR。uPAREMT。uPARRac130。1inhibitorofdifferentiation-1Id-1。Id-1N--RhoARac1EMT31。5．3Rac1Rac1AP-1MMP-2、32-33。RasGTPRasGTPase-activating-likeproteinIQGAP1Cdc42/Rac1Cdc42/Rac134。-。-PI3KRac1PANC-1MMP-235。TGF-beta1Rac1/ROS/NF-κB/IL-6/MMP-2SW199036。H-RasRac1MCF10A37-38。6RacRac1、、RacLimk1EMTGEFsuPARRac1。1HernándezEDeLaMota-PeynadoADharmawardhaneSetal．NovelinhibitorsofRac1inmetastaticbreastcancerJ．PRHealthSciJ2010294348-356．2NimnualASTaylorLJNyakoMetal．Perturbationofcy-toskeletondynamicsbytheopposingeffectsofRac1andRac1bJ．SmallGTPases20101289-97．3TanWPalmbyTRGavardJetal．AnessentialroleforRac1inendothelialcellfunctionandvasculardevelopmentJ．FASEBJ20082261829-1838．4SogaNConnollyJOChellaiahMetal．RacregulatesvascularendothelialgrowthfactorstimulatedmotilityJ．CellCommunAdhes2001811-13．5GarrettTAVanBuulJDBurridgeK．VEGF-inducedRac1acti-vationinendothelialcellsisregulatedbytheguaninenucleotideex-changefactorVav2J．ExpCellRes2007313153285-3297．6D'AmicoGRobinsonSDGermainMetal．Endothelial-Rac1isnotrequiredfortumorangiogenesisunlessalphavbeta3-integrinisabsentJ．PLoSOne201053e9766．7HunterSGZhuangGBrantley-SiedersDetal．EssentialroleofVavfamilyguaninenucleotideexchangefactorsinEphAreceptor-mediatedangiogenesisJ．MolCellBiol200626134830-4842．8Brantley-SiedersDMCaughronJHicksDetal．EphA2recep-tortyrosinekinaseregulatesendothelialcellmigrationandvascularassemblythroughphosphoinositide3-kinase-mediatedRac1GTPaseactivationJ．JCellSci2004117102037-2049．9．RhoGTPasesJ．2004269517-520．XUEYanBIFengLIUWenchaoetal．Expressionsandactivi-tiesofRhoGTPasesinhypoxiaanditsrelationshipwithtumoran-giogenesisJ．ChineseJournalofOncology2004269517-520．10MaQCavallinLEYanBetal．Antitumorigenesisofantioxida-ntsinatransgenicRac1modelofKaposi’ssarcomaJ．ProcNatlAcadSciUSA2009106218683-8688．11CaldasHFangusaroJRBoueDRetal．DissectingtheroleofendothelialsurvivindeltaEx3inangiogenesisJ．Blood200710941479-1489．12MallaRRGopi