LRP6 expression promotes cancer cell proliferation and tumorigenesis by altering beta-catenin subcellular distribution.
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 beta-catenin distribution such that the cytosolic beta-catenin level is significantly increased. This is accompanied by a significant increase in Wnt/beta-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/beta-catenin signaling.
Li
Yonghe
Y
Department of Pediatrics, St Louis Children's Hospital, Washington University School of Medicine, St Louis, MO 63110, USA. li_yo@kids.wustl.edu
Lu
Wenyan
W
He
Xi
X
Schwartz
Alan L
AL
Bu
Guojun
G
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000235:genetics*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D017931:DNA Primers; D006801:Humans; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011973:Receptors, LDL / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D017931:DNA Primers; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555476:Lrp6 protein, mouse; D011973:Receptors, LDL; D015534:Trans-Activators; D051176:beta Catenin