Department of Biochemistry and Molecular Biology, Drug Discovery Division, Southern Research Institute, Birmingham, AL 35255, United States.
FEBS Lett. 2011 Oct 3;585(19):3120-5. doi: 10.1016/j.febslet.2011.08.046. Epub 2011 Sep 5.
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.
Mesd 是 Wnt 共受体低密度脂蛋白受体相关蛋白-5（LRP5）和 LRP6 的一种特异性伴侣蛋白，它们的细胞外结构域包含四个β-螺旋桨/表皮生长因子模块，从 N 端到 C 端分别命名为 E1 到 E4。在此，我们证明重组 Mesd 蛋白是一种普遍的 Wnt 抑制剂，不仅能阻断 LRP6 E1-E2 结合 Wnt 诱导的 Wnt/β-catenin 信号，还能阻断 LRP6 E3-E4 结合 Wnt 诱导的 Wnt/β-catenin 信号。我们还发现 Mesd 能抑制前列腺癌 PC-3 细胞中 Wnt1 诱导的 Wnt/β-catenin 信号，并抑制 PC-3 异种移植模型中的肿瘤生长。我们的结果表明，Mesd 是细胞表面 Wnt/LRP 信号的通用抑制剂。
