IJMS, Vol. 20, Pages 5684: The Alteration of CTNNBIP1 in Lung Cancer (International Journal of Molecular Sciences)

β-catenin is a major component of the Wnt/β-catenin signaling pathway, and is known to play a role in lung tumorigenesis. β-catenin-interacting protein 1 (CTNNBIP1) is a known repressor of β-catenin transactivation. However, little is known about the role of CTNNBIP1 in lung cancer. The aim of this study was to carry out a molecular analysis of CTNNBIP1 and its effect on β-catenin signaling, using samples from lung cancer patients and various lung cancer cell lines. Our results indicate a significant inverse correlation between the CTNNBIP1 mRNA expression levels and the CTNNBIP1 promoter hypermethylation, which suggests that the promoter hypermethylation is responsible for the low levels of CTNNBIP1 present in many lung cancer patient samples. The ectopic expression of CTNNBIP1 is able to reduce the β-catenin transactivation; this then brings about a decrease in the expression of β-catenin-targeted genes, such as matrix metalloproteinase 7 (MMP7). Conversely, CTNNBIP1 knockdown is able to increase β-catenin transactivation and the expression of MMP7. In agreement with these findings, a low level of CTNNBIP1 was found to be correlated with a high level of MMP7 when a publicly available microarray dataset for lung cancer was analyzed. Also, in agreement with the above, the ectopic expression of CTNNBIP1 inhibits the migration of lung cancer cells, whereas the CTNNBIP1 knockdown increases cancer cell migration. Our findings suggest that CTNNBIP1 is a suppressor of cancer migration, thus making it a potential prognostic predictor for lung cancer.