EPS8L2 drives colorectal cancer cell proliferation and migration via YBX1-dependent activation of G3BP2 transcription
Abstract Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, characterized by molecular heterogeneity and limited therapeutic options. Here, we identified EPS8L2 as a novel driver of colorectal tumorigenesis. EPS8L2 is significantly upregulated in CRC tissues and n...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-08-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07929-x |
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| author | Yimeng Duan Peixian Li Yanmei Yang Guanghua Wu Hao Xing Hong Chen Liangbo Zhao Lei Liu Xiao Sun Shuiling Jin Luyun He Benyu Liu |
| author_facet | Yimeng Duan Peixian Li Yanmei Yang Guanghua Wu Hao Xing Hong Chen Liangbo Zhao Lei Liu Xiao Sun Shuiling Jin Luyun He Benyu Liu |
| author_sort | Yimeng Duan |
| collection | DOAJ |
| description | Abstract Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, characterized by molecular heterogeneity and limited therapeutic options. Here, we identified EPS8L2 as a novel driver of colorectal tumorigenesis. EPS8L2 is significantly upregulated in CRC tissues and negatively correlated with patients’ prognosis. Functionally, upregulation of EPS8L2 promotes proliferation and metastasis of CRC cells in vitro and in vivo, and vice versa. Similarly, EPS8L2 overexpression promotes patient-derived organoids growth. Mechanistically, EPS8L2 increases YBX1 phosphorylation by enhancing its interaction with phosphokinase S6K1. Phosphorylated YBX1 translocates into nucleus and initiates G3BP2 transcription, leading to activation of the MAPK signaling pathway. Moreover, knockout of Eps8l2 impairs CRC tumorigenesis in the AOM/DSS induced mouse model. In summary, we revealed a novel EPS8L2-YBX1-G3BP2 regulatory axis involved in CRC progression, which provides a new theoretical basis for tumor therapy. |
| format | Article |
| id | doaj-art-d09f8f5781d74774b772902e22e191c8 |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-d09f8f5781d74774b772902e22e191c82025-08-20T03:42:07ZengNature Publishing GroupCell Death and Disease2041-48892025-08-0116111610.1038/s41419-025-07929-xEPS8L2 drives colorectal cancer cell proliferation and migration via YBX1-dependent activation of G3BP2 transcriptionYimeng Duan0Peixian Li1Yanmei Yang2Guanghua Wu3Hao Xing4Hong Chen5Liangbo Zhao6Lei Liu7Xiao Sun8Shuiling Jin9Luyun He10Benyu Liu11State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou UniversityState Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou UniversityState Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou UniversityState Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou UniversityState Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou UniversityState Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou UniversityState Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou UniversityDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou UniversityState Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou UniversityDepartment of Oncology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou UniversityState Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou UniversityAbstract Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, characterized by molecular heterogeneity and limited therapeutic options. Here, we identified EPS8L2 as a novel driver of colorectal tumorigenesis. EPS8L2 is significantly upregulated in CRC tissues and negatively correlated with patients’ prognosis. Functionally, upregulation of EPS8L2 promotes proliferation and metastasis of CRC cells in vitro and in vivo, and vice versa. Similarly, EPS8L2 overexpression promotes patient-derived organoids growth. Mechanistically, EPS8L2 increases YBX1 phosphorylation by enhancing its interaction with phosphokinase S6K1. Phosphorylated YBX1 translocates into nucleus and initiates G3BP2 transcription, leading to activation of the MAPK signaling pathway. Moreover, knockout of Eps8l2 impairs CRC tumorigenesis in the AOM/DSS induced mouse model. In summary, we revealed a novel EPS8L2-YBX1-G3BP2 regulatory axis involved in CRC progression, which provides a new theoretical basis for tumor therapy.https://doi.org/10.1038/s41419-025-07929-x |
| spellingShingle | Yimeng Duan Peixian Li Yanmei Yang Guanghua Wu Hao Xing Hong Chen Liangbo Zhao Lei Liu Xiao Sun Shuiling Jin Luyun He Benyu Liu EPS8L2 drives colorectal cancer cell proliferation and migration via YBX1-dependent activation of G3BP2 transcription Cell Death and Disease |
| title | EPS8L2 drives colorectal cancer cell proliferation and migration via YBX1-dependent activation of G3BP2 transcription |
| title_full | EPS8L2 drives colorectal cancer cell proliferation and migration via YBX1-dependent activation of G3BP2 transcription |
| title_fullStr | EPS8L2 drives colorectal cancer cell proliferation and migration via YBX1-dependent activation of G3BP2 transcription |
| title_full_unstemmed | EPS8L2 drives colorectal cancer cell proliferation and migration via YBX1-dependent activation of G3BP2 transcription |
| title_short | EPS8L2 drives colorectal cancer cell proliferation and migration via YBX1-dependent activation of G3BP2 transcription |
| title_sort | eps8l2 drives colorectal cancer cell proliferation and migration via ybx1 dependent activation of g3bp2 transcription |
| url | https://doi.org/10.1038/s41419-025-07929-x |
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