1. ¹Department of Pediatrics, St Louis Children's Hospital, Washington University School of Medicine, St Louis, MO 63110, USA
2. ²Division of Neuroscience, Children's Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
3. ³Department of Molecular Biology and Pharmacology, St Louis Children's Hospital, Washington University School of Medicine, St Louis, MO 63110, USA
4. ⁴Department of Cell Biology and Physiology, St Louis Children's Hospital, Washington University School of Medicine, St Louis, MO 63110, USA

Correspondence: Y Li, Department of Pediatrics, Washington University School of Medicine, CB 8208, 660 South Euclid Avenue, St Louis, MO 63110, USA. E-mail: li_yo@kids.wustl.edu

Received 13 May 2004; Revised 22 July 2004; Accepted 22 July 2004; Published online 25 October 2004.

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 -catenin distribution such that the cytosolic -catenin level is significantly increased. This is accompanied by a significant increase in Wnt/-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/-catenin signaling.