CTTN促進(jìn)食管癌侵襲轉(zhuǎn)移的分子機(jī)制研究.pdf

1、北京協(xié)和醫(yī)學(xué)院(中國醫(yī)學(xué)科學(xué)院)博士學(xué)位論文CTTN促進(jìn)食管癌侵襲轉(zhuǎn)移的分子機(jī)制研究姓名：楊海申請學(xué)位級別：博士專業(yè)：細(xì)胞生物學(xué)指導(dǎo)教師：王明榮；林晨；劉芝華201005北京協(xié)和醫(yī)學(xué)院中國醫(yī)學(xué)科學(xué)院博士研究生學(xué)位論文AbstractMolecularMechanismsInVolVedinEsophagealSquamousCellCarcinomaMetastasisPromotedbyCTTNPhDCandidate：HaiYang

2、SuperVisor：MingRongN‰gstateKeyLaborato巧ofMolecularOncoIog蜘C鋤cerInstitute(Hospital)，PekingUnionMedicalCollege觚dChineSeAcademyofMedicalSciences，Beijingl0002lThecortactin(C刀Ⅳ夕gene10catesatllq13inhum鋤chromosomesandtheC丌Nprot

3、einconsistsoffivedomainswhicharen鋤edasN1A，REPEAT’HeIix，PRDandSH3inorder仔omtheN—tenninustomeC—terminusoftheprotcinOurpreviousStudyfoundthatf沱quent舢plification鋤dincreasedexpressionofC1TNinESCCcancertissueswasassociatedposi

4、tiveIywithlymphnodemetaStasisandtumorclinicalstagesFunctional鋤alysisindicatedthatCrrNenhancedabilitiesofmotility，inVasionand卸oikisresistance加dactivatedAKTsignalingpathwayinESCCcelllinesHoweVer’t11eextensionalnlolecuIarnl

5、echanismofClTN矗Jnctionremainsunkno、vnInthepresentSmdy，GSTpulldo、】vnwasperf0啪edwiththeC—tenninusdomainofC11Nprotein硒abaitt0precipitatetheCTTNinteractingprotcins，whichwereidentifiedbym蕊sspectmmSo妣theinteractionsbe鉚eenC訂N觚d

6、22candidatesoutofalltlIe23identifiedp∞teinshaVenotbeenreponedWeselectedZYX，IQGAPl，ASPP2，SH3Dl9鋤dKIAAl522for向rtherstudyItw勰obSen，cdthatZYX，lQGAPl鋤dKIAAl522colocalizedtogetherwithC1vl’NinESCCcesZYX，IQGAPlandASPP2couldbeco—

7、immunoprecipi協(xié)tedwithC1’INWbcarriedout向nctionanaIysisincellsofZYX鋤dIQGAPl，whichcouldbebothcolocalizedandcoimmunoprecipitatedwithCTrNThercsultsdemos仃；缸edthatinhibitcdZYXeXprcssiondecreaSedthecelIadhesiona11dmigrationabili

8、ty鯽dsuppressedIQGAPlexprcssionanenuated鋤。赫srcsist鋤ceoftumorcellsItw∞如nherdetectedinfluorcscence佗son鋤ceenergynans佗r(FRET)aSsaythatZYXintemctedwithCTlNinadillectway，whilelQGAPlmayinteractwithC1TNindirectlyMappinganalysissh