Disruption of β-Catenin Destruction Complex by Ephexin1-Axin1 Interaction Promotes Colorectal Cancer Proliferation

Wnt signaling is essential for cell growth and tumor formation, and is abnormally activated in colorectal cancer (CRC), contributing to tumor progression, but the specific role and regulatory mechanisms in tumor development are not yet clear. Here we show that Ephexin1, a guanine nucleotide exchange factor, is significantly overexpressed in CRC, correlating with increased Wnt/β-catenin pathway activity. Through comprehensive analysis, including RNA sequencing data from TCGA and functional assays, we demonstrated that Ephexin1 promotes tumor proliferation and migration by activating the Wnt/β-catenin pathway. This effect is mediated by the interaction of Ephexin1 with Axin1, a critical component of the β-catenin destruction complex, which in turn enhances stability and activity of β-catenin in signaling pathways critical for tumor development. Importantly, our findings also suggest that targeting Ephexin1 could enhance the efficacy of Wnt/β-catenin pathway inhibitors in CRC treatment. These findings highlight the potential of targeting Ephexin1 as a strategy for developing effective treatments for CRC, suggesting a novel and promising approach to therapy aimed at inhibiting cancer progression