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dc.contributor.authorJay, Steven M.
dc.contributor.authorKurtagic, Elma
dc.contributor.authorAlvarez, Luis M.
dc.contributor.authorDe Picciotto, Seymour
dc.contributor.authorHawkins, Jessica F.
dc.contributor.authorPrince, Robin N.
dc.contributor.authorGuerrero, Yadir
dc.contributor.authorTreasure, Carolyn L.
dc.contributor.authorLee, Richard T.
dc.contributor.authorGriffith, Linda G.
dc.contributor.authorSanchez, Edgar
dc.date.accessioned2012-12-18T20:14:10Z
dc.date.available2012-12-18T20:14:10Z
dc.date.issued2011-05
dc.date.submitted2011-05
dc.identifier.issn0021-9258
dc.identifier.issn1083-351X
dc.identifier.urihttp://hdl.handle.net/1721.1/75785
dc.description.abstractThe ErbB receptor family is dysregulated in many cancers, and its therapeutic manipulation by targeted antibodies and kinase inhibitors has resulted in effective chemotherapies. However, many malignancies remain refractory to current interventions. We describe a new approach that directs ErbB receptor interactions, resulting in biased signaling and phenotypes. Due to known receptor-ligand affinities and the necessity of ErbB receptors to dimerize to signal, bivalent ligands, formed by the synthetic linkage of two neuregulin-1β (NRG) moieties, two epidermal growth factor (EGF) moieties, or an EGF and a NRG moiety, can potentially drive homotypic receptor interactions and diminish formation of HER2-containing heterodimers, which are implicated in many malignancies and are a prevalent outcome of stimulation by native, monovalent EGF, or NRG. We demonstrate the therapeutic potential of this approach by showing that bivalent NRG (NN) can bias signaling in HER3-expressing cancer cells, resulting in some cases in decreased migration, inhibited proliferation, and increased apoptosis, whereas native NRG stimulation increased the malignant potential of the same cells. Hence, this new approach may have therapeutic relevance in ovarian, breast, lung, and other cancers in which HER3 has been implicated.en_US
dc.language.isoen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology (ASBMB)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1074/jbc.M111.221093en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alike 3.0en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en_US
dc.sourcePMCen_US
dc.titleEngineered Bivalent Ligands to Bias ErbB Receptor-mediated Signaling and Phenotypesen_US
dc.typeArticleen_US
dc.identifier.citationJay, S. M. et al. “Engineered Bivalent Ligands to Bias ErbB Receptor-mediated Signaling and Phenotypes.” Journal of Biological Chemistry 286.31 (2011): 27729–27740. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Center for Gynepathology Researchen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorJay, Steven M.
dc.contributor.mitauthorKurtagic, Elma
dc.contributor.mitauthorAlvarez, Luis M.
dc.contributor.mitauthorDe Picciotto, Seymour
dc.contributor.mitauthorSanchez Palacios, Edgar I.
dc.contributor.mitauthorPrince, Robin N.
dc.contributor.mitauthorGuerrero, Yadir
dc.relation.journalJournal of Biological Chemistryen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsJay, S. M.; Kurtagic, E.; Alvarez, L. M.; de Picciotto, S.; Sanchez, E.; Hawkins, J. F.; Prince, R. N.; Guerrero, Y.; Treasure, C. L.; Lee, R. T.; Griffith, L. G.en
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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