Kallistatin antagonizes Wnt/β-catenin signaling and cancer cell motility via binding to low-density lipoprotein receptor-related protein 6

被引:2
|
作者
Jingmei Zhang
Zhirong Yang
Pengfei Li
Grant Bledsoe
Lee Chao
Julie Chao
机构
[1] Medical University of South Carolina,Department of Biochemistry and Molecular Biology
[2] Charleston Southern University,Department of Biology
来源
Molecular and Cellular Biochemistry | 2013年 / 379卷
关键词
Kallistatin; LRP6; Wnt; β-catenin;
D O I
暂无
中图分类号
学科分类号
摘要
Kallistatin, a plasma protein, exerts pleiotropic effects in inhibiting angiogenesis, inflammation and tumor growth. Canonical Wnt signaling is the primary pathway for oncogenesis in the mammary gland. In this study, we demonstrate that kallistatin bound to the Wnt coreceptor low-density lipoprotein receptor-related protein 6 (LRP6), thus, blocking Wnt/β-catenin signaling and Wnt-mediated growth and migration in MDA-MB-231 breast cancer cells. Kallistatin inhibited Wnt3a-induced proliferation, migration, and invasion of cultured breast cancer cells. Moreover, kallistatin was bound to LRP6 in breast cancer cells, as identified by immunoprecipitation followed by western blot. Kallistatin suppressed Wnt3a-mediated phosphorylation of LRP6 and glycogen synthase kinase-3β, and the elevation of cytosolic β-catenin levels. Furthermore, kallistatin antagonized Wnt3a-induced expression of c-Myc, cyclin D1, and vascular endothelial growth factor. These findings indicate a novel role of kallistatin in preventing breast tumor growth and mobility by direct interaction with LRP6, leading to blockade of the canonical Wnt signaling pathway.
引用
收藏
页码:295 / 301
页数:6
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