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LRP5/6 directly bind to Frizzled and prevent Frizzled-regulated tumour metastasis

Author

Listed:
  • Dan-ni Ren

    (Clinical and Translational Research Center Shanghai East Hospital, Key Laboratory of Arrhythmias of Ministry of Education)

  • Jinxiao Chen

    (Tongji University School of Medicine)

  • Zhi Li

    (Chiba University Graduate School of Medicine)

  • Hongwei Yan

    (Tongji University School of Medicine)

  • Yan Yin

    (Clinical and Translational Research Center Shanghai East Hospital, Key Laboratory of Arrhythmias of Ministry of Education)

  • Da Wo

    (Tongji University School of Medicine)

  • Jiankang Zhang

    (Tongji University School of Medicine)

  • Luoquan Ao

    (Tongji University School of Medicine)

  • Bo Chen

    (Clinical and Translational Research Center Shanghai East Hospital, Key Laboratory of Arrhythmias of Ministry of Education)

  • Takashi K. Ito

    (Chiba University Graduate School of Medicine)

  • Yihan Chen

    (Clinical and Translational Research Center Shanghai East Hospital, Key Laboratory of Arrhythmias of Ministry of Education
    Tongji University School of Medicine)

  • Zhongmin Liu

    (Clinical and Translational Research Center Shanghai East Hospital, Key Laboratory of Arrhythmias of Ministry of Education)

  • Yongyong Li

    (Tongji University School of Medicine)

  • Jianhua Yang

    (Tongji University School of Medicine)

  • Xiaoling Lu

    (Biological Targeting Diagnosis and Therapy Research Center, Guangxi Medical University)

  • Yi Peng

    (Biological Targeting Diagnosis and Therapy Research Center, Guangxi Medical University)

  • Linghui Pan

    (The Affiliated Tumor Hospital, Guangxi Medical University)

  • Yongxiang Zhao

    (Biological Targeting Diagnosis and Therapy Research Center, Guangxi Medical University)

  • Shangfeng Liu

    (Clinical and Translational Research Center Shanghai East Hospital, Key Laboratory of Arrhythmias of Ministry of Education
    Tongji University School of Medicine)

  • Weidong Zhu

    (Clinical and Translational Research Center Shanghai East Hospital, Key Laboratory of Arrhythmias of Ministry of Education
    Tongji University School of Medicine)

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.

Suggested Citation

  • Dan-ni Ren & Jinxiao Chen & Zhi Li & Hongwei Yan & Yan Yin & Da Wo & Jiankang Zhang & Luoquan Ao & Bo Chen & Takashi K. Ito & Yihan Chen & Zhongmin Liu & Yongyong Li & Jianhua Yang & Xiaoling Lu & Yi , 2015. "LRP5/6 directly bind to Frizzled and prevent Frizzled-regulated tumour metastasis," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7906
    DOI: 10.1038/ncomms7906
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