| Literature DB >> 25902418 |
Dan-Ni Ren1, Jinxiao Chen2, Zhi Li3, Hongwei Yan2, Yan Yin1, Da Wo2, Jiankang Zhang2, Luoquan Ao2, Bo Chen1, Takashi K Ito3, Yihan Chen4, Zhongmin Liu1, Yongyong Li2, Jianhua Yang2, Xiaoling Lu5, Yi Peng5, Linghui Pan6, Yongxiang Zhao5, Shangfeng Liu4, Weidong Zhu4.
Abstract
How Wnt signalling including canonical and non-canonical pathways are initiated at the cell surface is not completely understood. Here we report that Wnt receptor Frizzled (Frz) and theco-receptors LRP5 and LRP6 (LRP5/6) directly interact with each other and this interaction is regulated by the LRP6 ectodomain. Importantly, through direct binding to Frz, LRP5/6 are able to prevent Frz-regulated non-canonical pathway activation and further non-canonical pathway-mediated tumour metastasis. Knockdown of endogenous LRP5/6 promotes otherwise-nonaggressive tumour cells to migrate in vitro, whereas a soluble recombinant protein of LRP6 ectodomain suppresses migration and metastasis of otherwise-aggressive tumour cells in vitro and in vivo. Furthermore, the expression level of membrane LRP5/6 correlates inversely with metastasis in mouse and human breast cancer. Our study suggests a previously unrecognized mode of receptor interaction, revealing the mechanism of LRP5/6 in inhibition of non-canonical pathway, and a possible clinical use of the LRP6 ectodomain to impede metastasis.Entities:
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Year: 2015 PMID： 25902418 DOI： 10.1038/ncomms7906
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919