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

Author:
Lin, Cuihong, Lu, Wenyan, Zhai, Ling, Bethea, Traci, Berry, Kristy, Qu, Zhican, Waud, William R., Li, Yonghe
Source:
FEBS letters 2011 v.585 no.19 pp. 3120-3125
ISSN:
0014-5793
Subject:
low density lipoprotein, models, prostatic neoplasms
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.
Agid:
983377