Disruption of the β-catenin destruction complex via 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; however, the specific role and regulatory mechanisms involved in tumor development remain unclear. Here, we show that Ephexin1, a guanine nucleotide exchange factor, is significantly overexpressed in CRC and is correlated with increased Wnt/β-catenin pathway activity. Through comprehensive analysis, including RNA sequencing data from TCGA and functional assays, we observed that Ephexin1 promotes tumor proliferation and migration by activating the Wnt/β-catenin pathway. This effect was mediated by the interaction of Ephexin1 with Axin1, a critical component of the β-catenin destruction complex, which in turn enhanced the stability and activity of β-catenin in signaling pathways critical for tumor development. Importantly, our findings also suggest that targeting Ephexin1 may increase 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. Wnt signaling is crucial for cell growth and is often overactive in cancers like colorectal cancer (CRC). This study explores the role of a protein called Ephexin1 in CRC. Researchers found that Ephexin1 is overexpressed in CRC and promotes tumor growth by activating Wnt/β-catenin signaling. They used various cell lines and animal models to study this interaction. The study involved analyzing gene expression data from The Cancer Genome Atlas (TCGA) and conducting experiments to understand how Ephexin1 affects β-catenin stability, a key player in Wnt signaling. Results showed that reducing Ephexin1 levels made CRC cells more sensitive to Wnt inhibitors, suggesting that targeting Ephexin1 could enhance treatment efficacy. The researchers conclude that Ephexin1 is a potential therapeutic target for CRC, as it plays a significant role in Wnt signaling modulation. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.