Catenin acts as a tumor suppressor through context-dependent mechanisms in colorectal cancer

Purpose [gamma]-Catenin is a protein closely related to [beta]-catenin. While the overexpression of [beta]-catenin has been linked with impaired prognosis and survival in various malignancies, both oncogenic and tumor suppressor functions have been described for [gamma]-catenin. Thus, its role in cancer remains controversial. In this study, we examined the impact of [gamma]-catenin expression on the malignant potential of colorectal cancer cells. Methods [gamma]-Catenin was knocked down by short interfering RNA in the [gamma]-catenin-proficient DLD-1 cell line and stably overexpressed in the [gamma]-catenin-deficient cell line RKO. The effects of these molecular manipulations on the malignant potential of the cell lines were tested in vitro and in vivo in a xenograft tumor model. Results [gamma]-Catenin contributed to Wnt signaling independent of the cellular context. Unlike its sister molecule [beta]-catenin, [gamma]-catenin inhibited cellular invasion and anoikis in cells endogenously expressing [gamma]-catenin. In line with this tumor suppressor function, its de novo expression in RKO cells inhibited proliferation via cell cycle arrest. In a xenograft tumor model, overexpression of [gamma]-catenin starkly reduced tumor growth in vivo. Conclusions This is the first report demonstrating a tumor-suppressive effect of [gamma]-catenin in colorectal cancer both in vitro and in vivo. Detailed in vitro analysis revealed that effects of [gamma]-catenin differ in [gamma]-catenin proficient and deficient cells, indicating that its function in colorectal cancer is dependent on the cellular context. This finding adds to our understanding of [gamma]-catenin and may have implications for future studies of catenin/Wnt targeted cancer therapies.