Beta-catenin is a multifunctional protein acting as a key factor in the cadherin-mediated
cell-cell adhesion system and in the Wnt signaling pathway. To demonstrate the molecular
mechanisms of metastasis of hepatocellular carcinoma (HCC) cells, we established a
metastatic subclone of human HCC H7402 cells, termed M-H7402, by isolating from transplantation
of H7402 cells into severe combined immunodeficient (SCID) mice. Based on the 2 parallel
cell lines, we investigated the roles of dickkopf-1 (Dkk-1) and Wnt/beta-catenin pathway
in proliferation and migration of HCC cells. cDNA microarray showed that 24 genes
were related to tumor metastasis differentially expressed between H7402 and M-H7402
cells. Western blot analysis revealed that the expression levels of beta-catenin,
c-Myc, and cyclin D1 were upregulated, but Dkk-1 and nm23 were dramatically downregulated
in M-H7402 cells, which suggests that the 2 cell lines were remarkably different in
molecular events associated with metastasis. Furthermore, we found that overexpression
of Dkk-1 by transfection was able to downregulate the expression of c-Myc and cyclin
D1, and it also inhibited the growth and migration in M-H7402 cells. Although reduction
of Dkk-1 expression by RNA interference was able to upregulate the expression of beta-catenin,
c-Myc, and cyclin D1 in H7402 cells, it also promoted beta-catenin translocation from
cytoplasm into nuclei and increased the migration of the cells. Therefore, we conclude
that Dkk-1/Wnt/beta-catenin cascade may mediate the proliferation and migration of
HCC cells during the metastasis process.