Breast Cancer Stem Cells Survive Periods of Farnesyl-Transferase Inhibitor-Induced Dormancy by Undergoing Autophagy英文文献资料.docVIP

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Breast Cancer Stem Cells Survive Periods of Farnesyl-Transferase Inhibitor-Induced Dormancy by Undergoing Autophagy英文文献资料.doc

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Breast Cancer Stem Cells Survive Periods of Farnesyl-Transferase Inhibitor-Induced Dormancy by Undergoing Autophagy英文文献资料

HindawiPublishingCorporation BoneMarrowResearch Volume2011,ArticleID362938,7pages doi:10.1155/2011/362938 ResearchArticle BreastCancerStemCellsSurvivePeriodsofFarnesyl-Transferase Inhibitor-InducedDormancybyUndergoingAutophagy MoumitaChaterjee1,2andKennethL.vanGolen 1,2 1 TheLaboratoryofCytoskeletalPhysiology,DepartmentofBiologicalSciences,UniversityofDelaware,Newark, DE19716,USA 2 TheCenterForTranslationalCancerResearch,UniversityofDelaware,320WolfHall,Newark,DE19716,USA CorrespondenceshouldbeaddressedtoKennethL.vanGolen,klvg@ Received15February2011;Accepted18May2011 AcademicEditor:RossBrown Copyright?2011M.ChaterjeeandK.L.vanGolen. This is an open access article distributed under the Creative Commons AttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkis properlycited. Acancerstemcellhasbeende?nedasacellwithinatumorthatpossessesthecapacitytoself-renewandtocausetheheterogeneous lineagesofcancercellsthatcomprisethetumor.Thesetumor-formingcellscouldhypotheticallyoriginatefromstem,progenitor, ordi?erentiatedcells.Previously,wehaveshownthatbreastcancercellswith lowmetastaticpotentialcanbeinducedintoa reversiblestateofdormancybyfarnesyltransferaseinhibitors(FTIs).DormancywasinducedbychangesinRhoAandRhoC GTPases.Speci?cally,RhoAwasfoundtobehypoactivatedwhileRhoCwashyperactivated.Inthecurrentstudywedemonstrate thatthesedormantcellsalsoexpresscertainknownstemcellmarkerssuchasaldehydedehydrogenaseI(ALDHI)andclusterof di?erentiation44(CD44).WealsoshowthatautophagymarkersAtg5,Atg12,andLC3-Bareexpressedinthesedormantstemcell- likebreastcancercells.Inhibitingautophagybyinhibitor3-methyladenine(3-MA)blockedtheprocessofautophagyreversingthe dormantphenotype.Further,weshowthatc-junNH2terminalkinase(JNK/SAPK)isupregulatedinthesedormantstemcell-like breastcancercellsandisresponsibleforincreasingautophagy. 1.Introduction GTPasebecomeshyperactivated.Thesechangesleadtoradi- calchangesinthecellcytoskeletonandcellularmo