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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| Format: | Article |
| Language: | English |
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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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| author | Jeeho Kim Young Jin Jeon In-Youb Chang Jung-Hee Lee Ho Jin You |
| author_facet | Jeeho Kim Young Jin Jeon In-Youb Chang Jung-Hee Lee Ho Jin You |
| author_sort | Jeeho Kim |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e6bc391676bc429793933d5a8219ac1e |
| institution | Kabale University |
| issn | 2092-6413 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-e6bc391676bc429793933d5a8219ac1e2025-02-09T12:14:08ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132025-01-0157115116610.1038/s12276-024-01381-1Disruption of the β-catenin destruction complex via Ephexin1-Axin1 interaction promotes colorectal cancer proliferationJeeho Kim0Young Jin Jeon1In-Youb Chang2Jung-Hee Lee3Ho Jin You4Laboratory of Genomic Instability and Cancer TherapeuticsDepartment of PharmacologyDepartment of AnatomyLaboratory of Genomic Instability and Cancer TherapeuticsLaboratory of Genomic Instability and Cancer TherapeuticsAbstract 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.https://doi.org/10.1038/s12276-024-01381-1 |
| spellingShingle | Jeeho Kim Young Jin Jeon In-Youb Chang Jung-Hee Lee Ho Jin You Disruption of the β-catenin destruction complex via Ephexin1-Axin1 interaction promotes colorectal cancer proliferation Experimental and Molecular Medicine |
| title | Disruption of the β-catenin destruction complex via Ephexin1-Axin1 interaction promotes colorectal cancer proliferation |
| title_full | Disruption of the β-catenin destruction complex via Ephexin1-Axin1 interaction promotes colorectal cancer proliferation |
| title_fullStr | Disruption of the β-catenin destruction complex via Ephexin1-Axin1 interaction promotes colorectal cancer proliferation |
| title_full_unstemmed | Disruption of the β-catenin destruction complex via Ephexin1-Axin1 interaction promotes colorectal cancer proliferation |
| title_short | Disruption of the β-catenin destruction complex via Ephexin1-Axin1 interaction promotes colorectal cancer proliferation |
| title_sort | disruption of the β catenin destruction complex via ephexin1 axin1 interaction promotes colorectal cancer proliferation |
| url | https://doi.org/10.1038/s12276-024-01381-1 |
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