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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Cell Line, Tumor
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HEK293 Cells
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Humans
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Ligands*
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Low Density Lipoprotein Receptor-Related Protein-5 / genetics
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Low Density Lipoprotein Receptor-Related Protein-5 / metabolism*
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Low Density Lipoprotein Receptor-Related Protein-6 / genetics
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Low Density Lipoprotein Receptor-Related Protein-6 / metabolism*
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Male
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Mice
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Molecular Chaperones / genetics
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Molecular Chaperones / metabolism*
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology
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Signal Transduction / physiology*
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Transplantation, Heterologous
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Wnt Proteins / antagonists & inhibitors*
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Wnt Proteins / genetics
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Wnt Proteins / metabolism*
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beta Catenin / metabolism
Substances
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LRP5 protein, human
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LRP6 protein, human
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Ligands
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Low Density Lipoprotein Receptor-Related Protein-5
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Low Density Lipoprotein Receptor-Related Protein-6
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MESD protein, human
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Molecular Chaperones
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Wnt Proteins
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beta Catenin