预览加载中，请您耐心等待几秒...

Twist1在结直肠癌伊立替康耐药过程中的作用.docx

预览
1/3
2/3
3/3

在线预览结束，喜欢就下载吧，查找使用更方便

下载提示 文本预览

如果您无法下载资料，请参考说明：

1、部分资料下载需要金币，请确保您的账户上有足够的金币

2、已购买过的文档，再次下载不重复扣费

3、资料包下载后请先用软件解压，在使用对应软件打开

Twist1在结直肠癌伊立替康耐药过程中的作用 Title:TheRoleofTwist1intheDevelopmentofResistancetoErlotinibinColorectalCancer Introduction: Colorectalcancer(CRC)isoneofthemostcommonmalignanciesworldwide,withahighmortalityrate.Despiteadvancesintreatmentstrategies,acquiredresistancetotargetedtherapyremainsasignificantclinicalchallenge.Erlotinib,anepidermalgrowthfactorreceptor(EGFR)tyrosinekinaseinhibitor,hasshownpromisingresultsinCRCpatients.However,thedevelopmentofresistancetoerlotiniblimitsitsefficacy.Therefore,understandingthemolecularmechanismsunderlyingerlotinibresistanceiscrucialforthedevelopmentofmoreeffectivetherapeuticstrategies. Twist1anditsroleincancer: Twist1isatranscriptionfactorthatplaysacrucialroleinembryonicdevelopment,tissuedifferentiation,andmetastasis.Twist1isalsofrequentlyoverexpressedinvariouscancertypes,includingCRC.StudieshavedemonstratedthatTwist1promotescellmigration,invasion,andepithelial-to-mesenchymaltransition(EMT),aprocesslinkedtometastasisanddrugresistance.EMTinductionisassociatedwiththeacquisitionofstemcell-likepropertiesincancercells,leadingtotherapeuticresistanceandtumorrelapse. MechanismsofTwist1-mediatedresistancetoerlotinibinCRC: 1.ActivationofEGFRsignalingpathway: Twist1interactswithEGFR,leadingtotheactivationofdownstreamsignalingpathwaysinvolvedincellsurvival,proliferation,andresistancetoapoptosis.Thisactivationcanpromoteresistancetoerlotinib,asEGFRsignalingiscrucialforerlotinib'santicancereffects. 2.InductionofEMT: Twist1playsacrucialroleinEMTinduction,whichisassociatedwitherlotinibresistance.EMTcontributestothelossofepithelialcharacteristicsandacquisitionofmesenchymalproperties,leadingtoincreaseddrugresistanceandcancercellsurvival.Twist1promotestheexpressionofEMT-relatedtranscriptionfactors,suchasSnail,Slug,andZEB1,whichrepressE-cadherinexpressionandenhancemesenchymalmarkerexpression. 3.Enhancementofcancerstemcellproperties: Twist1regulatestheself-renewalandpluripotencyofcancerstemcells(CSCs).CSCsareasmallsubpopulationoftumorcellswithself-renewalandd