csc translational medicine强教授仅供参考不得及用于商业用途违者

Studyingprostatestemcellsandprostatecancerstemcellsbycelldivisionmode StateKeyLaboratoryofOncogenesandRelatedGenesMed-X-RenjiHospitalStemCellCenterSchoolofBiomedicalMay7,RoleofcelldivisionmodesinepithelialcelldevelopmentandtumorigenesisAndrogen-independenceofprostatecancerandpossiblenewmechanismsRoleofcelldivisionmodesinepithelialcelldevelopment,regenerationandAndrogen-independenceofprostatecancerandpossiblenewmechanismsCellDivisionModesofStem StemcellStemcellDifferentiateAbnormaldivisionmodesmayleadtotissuerepairdeficitsandtumorigenesis

AsymmetricalToomuchself-

Toolittleself-DepletionofstemUnderstandingoftheregulationmechanismofstemcelldivisionmodesisimportantParcomplexandasymmetricalstemcellTheimportanceofstudyingthecelldivisionmodesofm lianepithelialstemcellsThepaststudiesaremostlydoneinDrosophilaC.Sofar,studiesinthem liansystemaremainlydoneinthedevelo cortexorepidermisMosttissuescomposedofepithelialcellshaveregenerativeMostsolidtumorshaveanepithelial

Whatarethecelldivisionmodesduringprostatedevelopment?Basalcellsdisybothsymmetrical(horizontal)andasymmetrical(vertical)divisionsWangetal.,2014,NatureLuminalcellsshowmainlyhorizontaldivisionsandgiveriseonlytoluminalcellsWangetal.,2014,NatureBasalcelllineagetracerCK14-CreER/RosaRFPmiceprovideadditionalevidencefortheasymmetricaldivisionWangetal.,2014,Nature基底细胞和腔细胞具有不同的细胞极性方式Cell-of-originforprostatecancerisaninterestingresearchfocuspointWhichoftheepithelialcellsisthecell-of-originforprostateCanweexplorethisissuefromtheangleofcelldivisionWhatarethecelldivisionmodesduringprostatetumorigenesis?Prb-Cre;Ptenfl/flmiceprovideusagoodmodeltostudycelldivisionmodesinprostatetumorigenesisLossLossof PTENistheonlysingle-genedeletionthatdemonstratestumorpathologyintheprostate(Abate-Shen&Shen,2000;PTENistheonlysingle-genedeletionthatdemonstratestumorpathologyintheprostateTransformedluminalcellscandirectlygenerateprostatetumorsviasymmetricalcelldivisionsWangetal.,2014,NatureAtransformedbasalcellcanalsoatumorviaasymmetricalcelldivisiontogiverisetoadaughtertransformedluminalcellWangetal.,2014,NaturePtendeletionleadstothelossofpolarityoftheluminalcellsandthechangeofmitosisaxisWangetal.,2014,NatureBasalandluminalcellsshowdifferentpolarityandcelldivisionmodesintheprostateNewinsightsintoprostatedevelopmentandtumorigenesis(fromcelldivisionmodeangle)Roleofcelldivisionmodesinepithelialcelldevelopment,regenerationandAndrogen-independenceofprostatecancerandpossiblenewmechanisms 病率 肿

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生活方式变化 去势：切 药物：抗抗 疗法包括切 或服用药 依赖性可转变为非依赖性，即耐药癌的治疗瓶颈：A异常扩 B突 C交叉激？

以往研究聚焦点—— 受体（对激素敏感性增加 展提示与新思路— 癌 TwoTwoGeneticModelsforStemCellModel(akaHierarchicalTumorisOnlyasubsetofcellsistumor-initiating(cancerstemItispossibletopredictwhichcellswillbetumor-initiatingStochasticEverycellwithinatumorispotentiallytumor-Itisimpossibletopredictwhichcellswillbetumor-initiatingIdentificationofCancerStem1994:John2003:Michael2004:Peter2005:Tyler2005:Denis2007:John2007:Diane2008:Markus

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Reyaetal,2001,Androgen-independentCellsMightActasProstateAndrogen-independentCellsMightActasProstateCancerStem/Re-initiatingCellsEffectivelykilltumorcells&alleviatesMorebasal-likeandrogen-independentcellsOvertime,stemcellsortheirprogenygainabilitytoeandrogenindependent&repopulate

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Cancerstemcellconceptiscontroversial, definitioncanbe OriginaldefinitionforanddifferentiationcapabilityRecentlytheconceptisHighlytumor-HighlytherapeuticHighlyExperimentalDesignforAxenograftmodelforhumanprostatePassagedinvivo ntationinSimilarresponsetoandrogendeprivationasseeninhumansProduces因InvolvementofEmbryonic因 in

去势去势(Sunetal.,CancerResearchExpressionofEMTgenes/proteinsareelevatedinandrogen-independentprostatecancercells (Sunetal.,CancerResearchQuestionstobeWouldmodulatingEMTaffect deprivationtherapy? CanwereversethefeaturesofcancerstemcellsbyinhibitingOverexpressionofZeb1enhances toandrogenLietal.,Exp.Biol.Med.,Down-regulationofZEB1leadstoaninhibitiononDU145DU145**Lietal.,Exp.Biol.Med.,OverexpressionorknockdownofZeb1affectsthestemnessofprostatecancercellsLietal.,Exp.Biol.Med.,CanweidentifynovelmoleculesthatcontrolcelldivisionmodesandthenaffectthedevelopmentofcastrationofTOP2ATOP2ArankedattheverytopinsecondaryprostateHighTOP2AHighTOP2Aexpressionwaspositivelycorre