Abstract
BackgroundActivation of the Wnt/β-catenin signaling pathway plays a crucial role in hepatocellular carcinoma (HCC). Low-density lipoprotein (LDL) receptor-related protein-6 (LRP6) is one of the co-receptors of the Wnt/β-catenin pathway and forms a signaling complex with Wnt ligand and Frizzled receptor to activate downstream signaling. However, the role of LRP6 in hepatocarcinogenesis is unclear. In this study, we examined its expression and roles in human HCC.Methodology/Principal FindingsUsing real-time quantitative RT-PCR, we found that LRP6 was frequently (45%) overexpressed in human HCCs (P = 0.003). In vitro studies showed that ectopic expression of LRP6 increased the protein level of β-catenin. Moreover, overexpression of the full-length and constitutively active LRP6, respectively, activated the WNT/β-catenin signaling pathway, as shown by the TCF/β-catenin reporter assay. With regard to the effects of LRP6 overexpression in HCC cells, stable overexpression of the constitutively active LRP6 in BEL-7402 HCC cells enhanced cell proliferation, cell migration, and invasion in vitro as well as tumorigenicity in nude mice.Conclusions/SignificanceOur findings indicate that overexpression of LRP6 contributes to the hyperactivation of the Wnt/β-catenin signaling pathway in human HCCs and suggest it may play a role in hepatocarcinogenesis.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and prevalent in Eastern and Southeast Asia and Africa [1]
Conclusions/Significance: Our findings indicate that overexpression of LRP6 contributes to the hyperactivation of the Wnt/ b-catenin signaling pathway in human hepatocellular carcinoma (HCC) and suggest it may play a role in hepatocarcinogenesis
Our findings indicate that overexpression of LRP6 contributes to the hyperactivation of Wnt/b-catenin signaling pathway and suggest it plays a role in hepatocarcinogenesis
Summary
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and prevalent in Eastern and Southeast Asia and Africa [1]. Aberrant activation of Wnt/bcatenin signaling pathway is closely associated with the formation of HCC [2,3,4,5,6,7,8]. Upon Wnt activation, b-catenin is no longer targeted for degradation but accumulates in the cytoplasm and translocates into the nucleus. We reported that b-catenin gene mutations at exon 3 were found in about 12% in human HCCs and the mutations at this site contributed to accumulation of b-catenin in HCC [11]. Activation of the Wnt/b-catenin signaling pathway plays a crucial role in hepatocellular carcinoma (HCC). Lowdensity lipoprotein (LDL) receptor-related protein-6 (LRP6) is one of the co-receptors of the Wnt/b-catenin pathway and forms a signaling complex with Wnt ligand and Frizzled receptor to activate downstream signaling. We examined its expression and roles in human HCC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
