Requirement of Podocalyxin in TGF-Beta Induced Epithelial Mesenchymal Transition 英文参考文献.docVIP

RequirementofPodocalyxininTGF-BetaInduced EpithelialMesenchymalTransition XiaoboMeng1*,PeymanEzzati1,JohnA.Wilkins1,2 1Manitoba Centre for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada, 2Biochemistry and MedicalGenetics,UniversityofManitoba,Winnipeg,Manitoba,Canada Abstract Epithelial mesenchymal transition (EMT) is characterized by the development of mesenchymal properties such as a fibroblast-like morphology with altered cytoskeletal organization and enhanced migratory potential. We report that the expressionofpodocalyxin(PODXL),amemberoftheCD34family,ismarkedlyincreasedduringTGF-binducedEMT.PODXL isenrichedontheleadingedgesofmigratingA549cells.Silencingofpodocalyxinexpressionreducedcellruffleformation, spreading, migration and affected the expression patterns of several proteins that normally change during EMT (e.g., vimentin,E-cadherin).CytoskeletionassemblyinEMTwasalsofoundtobedependentontheproductionofpodocalyin. Compositional analysis of podocalyxin containing immunoprecipitates revealed that collagen type 1 was consistently associated with these isolates. Collagen type 1 was also found to co-localize with podocalyxin on the leading edges of migratingcells.Theinteractionswithcollagenmaybeacriticalaspectofpodocalyxinfunction.Podocalyxinisanimportant regulatoroftheEMTlikeprocessasitregulatesthelossofepithelialfeaturesandtheacquisitionofamotilephenotype. Citation: Meng X, Ezzati P, Wilkins JA (2011) Requirement of Podocalyxin in TGF-Beta Induced Epithelial Mesenchymal Transition. PLoS ONE 6(4): e18715. doi:10.1371/journal.pone.0018715 Editor:MichaelKlymkowsky,UniversityofColorado,Boulder,UnitedStatesofAmerica ReceivedOctober4,2010;AcceptedMarch16,2011;PublishedApril12,2011 Copyright: ? 2011 Meng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheorigina