Disruption of the β-catenin destruction complex via Ephexin1-Axin1 interaction promotes colorectal cancer proliferation
Abstract 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...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-01-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-024-01381-1 |
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| Summary: | Abstract 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. |
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| ISSN: | 2092-6413 |