β-Catenin-independent noncanonical Wnt pathway might be induced in gastric cancers.

BACKGROUND/AIMS: Abnormal Wnt signaling is often observed in human cancers. Wnt5a is a representative Wnt ligand that can activate both β-catenin-dependent canonical and β-catenin-independent noncanonical Wnt pathways. However, the role of Wnt5a in carcinogenesis is controversial. This study was designed to understand whether Wnt5a in the Wnt pathway and its key downstream molecules such as MMP-7 and β-catenin are involved in gastric cancers. METHODS: We analyzed the expressions of Wnt5a, MMP-7 and β-catenin genes in 40 primary gastric normal and tumor biopsies by RT-PCR and the subcellular localization of β-catenin by immunohistochemistry. RESULTS: Our results showed a specific combination of genes expressed significantly in the gastric tumor tissues: 65% of the tumor samples containing non-nuclear β-catenin were Wnt5a-positive, 42.5% were MMP-7-positive, and 35% of the samples involved both. Interestingly, normal samples did not show any relevant coexpression of Wnt5a and MMP-7 in the β-catenin-containing samples. CONCLUSIONS: These results suggest that the noncanonical Wnt pathway might be critically important in gastric carcinogenesis.