Cell Surface Cdc37 Participates in Extracellular HSP90 Mediated Cancer Cell Invasion 英文参考文献.docVIP

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Cell Surface Cdc37 Participates in Extracellular HSP90 Mediated Cancer Cell Invasion 英文参考文献.doc

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Cell Surface Cdc37 Participates in Extracellular HSP90 Mediated Cancer Cell Invasion 英文参考文献

CellSurfaceCdc37ParticipatesinExtracellularHSP90 MediatedCancerCellInvasion AvraamElHamidieh1,NicholasGrammatikakis2,EvangeliaPatsavoudi1,3* 1Department of Biochemistry, Hellenic Pasteur Institute, Athens, Greece, 2Institute of Biology, National Center for Scientific Research ‘‘Demokritos’’, Athens, Greece, 3DepartmentofBiomedicalInstrumentationTechnology,TechnologicalEducationalInstituteofAthens,Athens,Greece Abstract Cdc37 is a 50kDa molecular chaperone which targets intrinsically unstable protein kinases to the molecular chaperone HSP90.Itisalsoanover-expressedoncoproteinthatmediatescarcinogenesisandmaintenanceofthemalignantphenotype bystabilizingthecompromisedstructuresofmutantand/orover-expressedoncogenickinases.HerewereportthatCdc37 isnotrestrictedintracellularlybutinsteaditisalsopresentonthesurfaceofMDA-MB-453andMDA-MB-231humanbreast cancercells,whereitisshowntoparticipateincancercellmotilityprocesses.Furthermore,wedemonstrateusingananti- Cdc37 cell impermeable antibody, that similarly to its intracellular counterpart, this surface pool of Cdc37 specifically interactswithHSP90aswellasthekinasereceptorsHER2andEGFRonthecellsurface,probablyactingasaco-factorin HSP90’sextracellularchaperoningactivities.Finally,weshowthatfunctionalinhibitionofsurfaceHSP90usingmAb4C5,a cellimpermeablemonoclonalantibodyagainstthisprotein,leadsnotonlytodisruptionoftheCdc37/HSP90complexbut also to inhibition of the Cdc37/ErbB receptors complexes. These results support an essential role for surface Cdc37 in concertwithHSP90onthecellsurfaceduringcancercellinvasionprocessesandstrengthenthetherapeuticpotentialof mAb4C5forthetreatmentofcancer. Citation: El Hamidieh A, Grammatikakis N, Patsavoudi E (2012) Cell Surface Cdc37 Participates in Extracellular HSP90 Mediated Cancer Cell Invasion. PLoS ONE7(8):e42722.doi:10.1371/journal.pone.0042722 Editor:WanjinHong,InstituteofMolecularandCellBiology,Singapore ReceivedMarch29,2012;AcceptedJuly10,2012;PublishedAugust17,2012 Copyright:?2012ElHamid