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    FEBS Lett. 2011 Oct 3;585(19):3120-5. Epub 2011 Sep 5.

    Mesd is a general inhibitor of different Wnt ligands in Wnt/LRP signaling and inhibits PC-3 tumor growth in vivo.

    Lin C, Lu W, Zhai L, Bethea T, Berry K, Qu Z, Waud WR, Li Y.

    Source

    Department of Biochemistry and Molecular Biology, Drug Discovery Division, Southern Research Institute, Birmingham, AL 35255, United States.

    Abstract

    Mesd is a specialized chaperone for Wnt co-receptor low-density lipoprotein receptor-related protein-5 (LRP5) and LRP6, which contain four β-propeller/epidermal growth factor modules, named E1 to E4 from N- to C-terminal, in their extracellular domains. Herein, we demonstrated that recombinant Mesd protein is a general Wnt inhibitor that blocks Wnt/β-catenin signaling induced not only by LRP6 E1-E2-binding Wnts but also by LRP6 E3-E4-binding Wnts. We also found that Mesd suppressed Wnt/β-catenin signaling induced by Wnt1 in prostate cancer PC-3 cells, and inhibited tumor growth in PC-3 xenograft model. Our results indicate that Mesd is a universal inhibitor of Wnt/LRP signaling on the cell surface.

    Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

    PMID:
    21907199
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC3183310
    [Available on 2012/10/3]

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