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LRP6 expression promotes cancer cell proliferation and tumorigenesis by altering β-catenin subcellular distribution

Oncogene volume 23, pages 9129–9135 (2004)Cite this article

Abstract

The Wnt signaling pathway plays key roles in both embryogenesis and tumorigenesis. The low-density lipoprotein (LDL) receptor-related protein-6 (LRP6), a novel member of the expanding LDL receptor family, functions as an indispensable co-receptor for the Wnt signaling pathway. Although the role of LRP6 in embryonic development is now well established, its role in tumorigenesis is unclear. We report that LRP6 is readily expressed at the transcript level in several human cancer cell lines and human malignant tissues. Furthermore, using a retroviral gene transfer system, we find that stable expression of LRP6 in human fibrosarcoma HT1080 cells alters subcellular β-catenin distribution such that the cytosolic β-catenin level is significantly increased. This is accompanied by a significant increase in Wnt/β-catenin signaling and cell proliferation. Finally, we demonstrate that LRP6 expression promotes tumorigenesis in vivo. These results thus indicate that LRP6 may function as a potential oncogenic protein by modulating Wnt/β-catenin signaling.

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Acknowledgements

This work was supported in part by grant from the American Heart Association (0330118N) to YL, and grants from the National Institutes of Health to GB. GB is an Established Investigator of the American Heart Association. We are grateful to Dr Christof Niehrs for providing the LRP6 cDNA, and Dr Theodore C Simon for providing the cDNAs for human Wnt1 and β-catenin, and for the helpful discussion during the course of this study.

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Authors and Affiliations

  1. Department of Pediatrics, St Louis Children's Hospital, Washington University School of Medicine, St Louis, 63110, MO, USA

    Yonghe Li, Wenyan Lu, Alan L Schwartz & Guojun Bu

  2. Division of Neuroscience, Department of Neurology, Children's Hospital, Harvard Medical School, Boston, 02115, MA, USA

    Xi He

  3. Department of Molecular Biology and Pharmacology, St Louis Children's Hospital, Washington University School of Medicine, St Louis, 63110, MO, USA

    Alan L Schwartz

  4. Department of Cell Biology and Physiology, St Louis Children's Hospital, Washington University School of Medicine, St Louis, 63110, MO, USA

    Guojun Bu

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  1. Yonghe Li
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  2. Wenyan Lu
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Correspondence to Yonghe Li.

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Li, Y., Lu, W., He, X. et al. LRP6 expression promotes cancer cell proliferation and tumorigenesis by altering β-catenin subcellular distribution. Oncogene 23, 9129–9135 (2004). https://doi.org/10.1038/sj.onc.1208123

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