期刊
JOURNAL OF HEPATOLOGY
卷 48, 期 5, 页码 780-791出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2007.12.020
关键词
Wnt3; FZD7; hepatocellular carcinoma; canonical Wnt pathway
资金
- NCI NIH HHS [CA 35711, R37 CA035711, R01 CA035711] Funding Source: Medline
- NCRR NIH HHS [P20 RR015578-076550, P20 RR015578-086803, P20 RR015578, P20 RR 015578] Funding Source: Medline
- NIAAA NIH HHS [R37 AA002666, AA 02666, R01 AA002666] Funding Source: Medline
Background/Aims: The canonical Wnt signaling is frequently activated in human hepatocellular carcinoma (HCC). We previously demonstrated that upregulation of Frizzled-7 receptor (FZD7) in HCC was associated with nuclear accumulation of wild-type beta-catenin. Here, we investigated Wnt ligand(s) that may activate the Wnt/beta-catenin pathway through FZD7 in HCC cells. Methods: To identify Wnt ligand expression, RT-PCR was performed in HCC cells. To evaluate the function of Wnt3 and FZD7 in HCC, we utilized Wnt3 overexpressing FOCUS HCC cells (FOCUS-Wnt3) and human tumors. Results: In hepatitis B virus (HBV)-induced HCC, Wnt3 was upregulated in tumor and peritumoral tissues compared to normal liver and downstream beta-catenin target genes were also increased in these samples. Activation of the Wnt/beta-catenin pathway in FOCUS-Wnt3 cells was demonstrated by beta-catenin accumulation, enhanced TCF transcriptional activity and proliferation rate. The activation of Wnt/beta-catenin signaling in FOCUS-Wnt3 was abolished by a knockdown of FZD7 expression by siRNA. More important, a specific Wnt3-FZD7 interaction was observed by co-immunoprecipitation experiments, which suggest that the action of Wnt3 was mediated via FZD7. Conclusions: These findings demonstrate a functional interaction between Wnt3 and FZD7 leading to activation of the Wnt/beta-catenin signaling pathway in HCC cells and may play a role during hepatocarcinogenesis. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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