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《angiogenesis pathway》由会员上传分享，免费在线阅读，更多相关内容在行业资料-天天文库。
1、Angiogenesisisthe physiologicalprocessofthegrowthofnewbloodvesselsfrompre-existingvessels.Angiogenesiscanbeinducedbysolidtumorgrowth.Inthemeantime,angiogenesisprovidessolidtumorwithoxygenandnutrientstomakeitreachacertainsize.Therearemanyimportanttargetsrelatedtoangio
2、gensisincludingEGFR, HER2,VEGFR,PDGFR,FGFR,FLT3,HIF,ALK,VDA,S1Preceptor.Mostofthosetargetsarereceptortyrosinekinases(RTK)s.VascularEndothelialGrowthFactorReceptor(VEGFR)isthereceptorofVEGF.VEGFRisinvolvedincellproliferation,migration,survivalandpermeability.TheVEGFsi
3、ncludefiveknownstructurally-relatedmammalianligands(VEGFA,VEGFB,VEGFC,VEGFD,andplacentagrowthfactor,PLGF)andtherearealsothreestructurallyrelatedVEGFRssubtypes(VEGFR1,VEGFR2,andVEGFR3). EGFRisatrans-membranereceptorbelongingtotheerbB/HER-familyofRTK.EGFRexistsonthecel
4、lsurfaceandcanbeactivatedbyEGFandTGF-alpha.Manyimportantsignalingcascades,likeMAPK,Akt,andJNKpathways,couldbethedownstreamofEGFR. Erbb2(HER2) belongstoErbbfamilylacksthecapacitytointeractwithaligandbecauseitsextracellularregionexistsinafixed,unfoldedconformation.Erbb
5、2(HER2)actsasanamplifieroftheErbbsignalingnetwork.TheadaptorsandeffectorofErbb2includesShc,Syk,RasGAP,Grb2/7,Abl,Mapk8,PLCandSTAT1/3.Erbb3lackskinaseactivityandcanformheterodimericcomplexeswithErbb2.TheERBB2–ERBB3dimercanbeanimportantcancertherapeutictarget.Januskina
6、ses(JAKs)arenon-receptortyrosinekinaseswhichplaythekeyroleinJAK-STATsignalingpathway.AlargenumberofcytokinesdependonJAKincludinginterleukin(IL)-2,IL-4,IL-7,IL-9,IL-15andIL-21.Jakkinasesareinvolvedinmalignantcellgrowthandsurvival.Jakkinaseshavebeenshowntomodulateactiv
7、ationofRas-Raf-MAPkinasepathwayswhichareimplicatedinmalignanttransformation.ThefunctionofJakkinasesisalsorelatedtoAbl.Jakkinaseshavebeenalsoimplicatedintheregulationofp53-dependentcell-cyclearrestandapoptosis,forexample,JakkinasescanregulatethelevelsofBcl-XL,Bcl-2and
8、BaxexpressionbytheireffectsonStatsandotherreceptorlinkedpathwayssuchasthePI-3kinaseandtheRas-MAPKpathwaysTGF-beta/SmadTransformingG
