Kim M et al. - In a trial to investigate Wnt ligand(s) that may activate the Wnt/β-catenin pathway through Frizzled-7 receptor (FZD7) in hepatocellular carcinoma (HCC) cells, 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 Methods
To identify Wnt ligand expression, RT-PCR was performed in HCC cells
To evaluate the function of Wnt3 and FZD7 in HCC, Wnt3 overexpressing FOCUS HCC cells (FOCUS-Wnt3) and human tumors were utilized
Results
In hepatitis B virus (HBV)-induced HCC, Wnt3 was upregulated in tumor and peritumoral tissues compared to normal liver and downstream β-catenin target genes were also increased in these samples
Activation of the Wnt/β-catenin pathway in FOCUS-Wnt3 cells was demonstrated by β-catenin accumulation, enhanced TCF transcriptional activity, and proliferation rate
Activation of Wnt/β-catenin signaling in FOCUS-Wnt3 was abolished by a knockdown of FZD7 expression by siRNA
A specific Wnt3-FZD7 interaction was observed by co-immunoprecipitation experiments, suggesting that the action of Wnt3 was mediated via FZD7
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