CD44v6 Regulates Growth of Brain Tumor Stem Cells Partially through the AKT-Mediated Pathway 英文参考文献.docVIP

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CD44v6 Regulates Growth of Brain Tumor Stem Cells Partially through the AKT-Mediated Pathway 英文参考文献.doc

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CD44v6 Regulates Growth of Brain Tumor Stem Cells Partially through the AKT-Mediated Pathway 英文参考文献

CD44v6RegulatesGrowthofBrainTumorStemCells PartiallythroughtheAKT-MediatedPathway MayumiJijiwa1,HabibeDemir1,SnehalataGupta1,CrystalLeung2,KaushalJoshi1,NicholasOrozco3, TiffanyHuang4,VedatO.Yildiz5,IchiyoShibahara3,JasonA.deJesus4,WilliamH.Yong4,PaulS. Mischel4,SoledadFernandez5,HarleyI.Kornblum2,3,IchiroNakano1,6 * 1Department of Neurological Surgery, The Ohio State University, Columbus, Ohio, United States of America, 2Jonsson Comprehensive Cancer Center, David Geffen SchoolofMedicine,UniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesofAmerica,3DepartmentofMolecularandMedicalPharmacology,David GeffenSchoolofMedicine,UniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesofAmerica,4DepartmentofPathology,DavidGeffenSchoolof Medicine,University ofCalifornia Los Angeles, LosAngeles,California,United States ofAmerica, 5Center forBiostatistics,TheOhioStateUniversity,Columbus,Ohio, UnitedStatesofAmerica,6JamesComprehensiveCancerCenter,TheOhioStateUniversity,Columbus,Ohio,UnitedStatesofAmerica Abstract Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC) has gained substantial attention by scientistsandphysicians.However,themechanismoftumorinitiationandproliferationisstillpoorlyunderstood.CD44isa cellsurfaceproteinlinkedtotumorigenesisinvariouscancers.Inparticular,oneofitsvariantisoforms,CD44v6,isassociated withseveral cancer types. Todate itsexpression andfunctionin BTSCis yettobe identified. Here, wedemonstratethe presence and function of the variant form 6 of CD44 (CD44v6) in BTSC of a subset of glioblastoma multiforme (GBM). PatientswithCD44high GBMexhibitedsignificantlypoorerprognoses.Amongvariousvariantforms,CD44v6wastheonly isoformthatwasdetectedinBTSCanditsknockdowninhibitedinvitrogrowthofBTSCfromCD44high GBMbutnotfrom CD44lowGBM.Incontrast,thissiRNA-mediatedgrowthinhibitionwasnotapparentinthematchedGBMsamplethatdoes not possess stem-like properties. Stimulation with a CD44v6 ligand, os