UBE4B promotes gastric cancer proliferation and metastasis by mediating FAT4 ubiquitination and degradation
Abstract The ubiquitin‒proteasome system (UPS), an intracellular protein degradation pathway, plays an important role in regulating tumorigenesis and development. Ubiquitination factor E4B (UBE4B/UFD2) has been shown to be associated with the development of several cancers. The aim of this study was...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-07-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07794-8 |
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| author | Kaini Wu Zixiang Guo Yunfeng Fu Sicheng Yang Yating Pan Runwei Yan Xiaodong Zhou |
| author_facet | Kaini Wu Zixiang Guo Yunfeng Fu Sicheng Yang Yating Pan Runwei Yan Xiaodong Zhou |
| author_sort | Kaini Wu |
| collection | DOAJ |
| description | Abstract The ubiquitin‒proteasome system (UPS), an intracellular protein degradation pathway, plays an important role in regulating tumorigenesis and development. Ubiquitination factor E4B (UBE4B/UFD2) has been shown to be associated with the development of several cancers. The aim of this study was to reveal the functional significance of UBE4B in gastric cancer (GC) development and its important mechanism. Bioinformatics analysis, immunohistochemistry (IHC), western blotting, and real-time PCR were performed to detect UBE4B expression in human GC samples and GC cell lines and a mouse xenograft tumour model was established. Our investigation revealed that UBE4B is highly expressed in GC and promotes the proliferation, migration and invasion of GC cells. The quantitative Tandem Mass Tag (TMT) analysis revealed that FAT oncogenic homologue 4 (FAT4) is a downstream gene of UBE4B. Western blot experiments and transmission electron microscopy (TEM) results for biological samples revealed that UBE4B inhibits autophagy in GC cells and directly binds to and degrades FAT4 through ubiquitination. These results suggest that UBE4B can inhibit autophagy and promote GC progression by mediating FAT4 ubiquitination and degradation, and our findings provide a new potential therapeutic target for GC management. |
| format | Article |
| id | doaj-art-e7f13c82ce794b5db19786dcc2e3cb56 |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-e7f13c82ce794b5db19786dcc2e3cb562025-08-20T04:02:50ZengNature Publishing GroupCell Death and Disease2041-48892025-07-0116111610.1038/s41419-025-07794-8UBE4B promotes gastric cancer proliferation and metastasis by mediating FAT4 ubiquitination and degradationKaini Wu0Zixiang Guo1Yunfeng Fu2Sicheng Yang3Yating Pan4Runwei Yan5Xiaodong Zhou6Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityAbstract The ubiquitin‒proteasome system (UPS), an intracellular protein degradation pathway, plays an important role in regulating tumorigenesis and development. Ubiquitination factor E4B (UBE4B/UFD2) has been shown to be associated with the development of several cancers. The aim of this study was to reveal the functional significance of UBE4B in gastric cancer (GC) development and its important mechanism. Bioinformatics analysis, immunohistochemistry (IHC), western blotting, and real-time PCR were performed to detect UBE4B expression in human GC samples and GC cell lines and a mouse xenograft tumour model was established. Our investigation revealed that UBE4B is highly expressed in GC and promotes the proliferation, migration and invasion of GC cells. The quantitative Tandem Mass Tag (TMT) analysis revealed that FAT oncogenic homologue 4 (FAT4) is a downstream gene of UBE4B. Western blot experiments and transmission electron microscopy (TEM) results for biological samples revealed that UBE4B inhibits autophagy in GC cells and directly binds to and degrades FAT4 through ubiquitination. These results suggest that UBE4B can inhibit autophagy and promote GC progression by mediating FAT4 ubiquitination and degradation, and our findings provide a new potential therapeutic target for GC management.https://doi.org/10.1038/s41419-025-07794-8 |
| spellingShingle | Kaini Wu Zixiang Guo Yunfeng Fu Sicheng Yang Yating Pan Runwei Yan Xiaodong Zhou UBE4B promotes gastric cancer proliferation and metastasis by mediating FAT4 ubiquitination and degradation Cell Death and Disease |
| title | UBE4B promotes gastric cancer proliferation and metastasis by mediating FAT4 ubiquitination and degradation |
| title_full | UBE4B promotes gastric cancer proliferation and metastasis by mediating FAT4 ubiquitination and degradation |
| title_fullStr | UBE4B promotes gastric cancer proliferation and metastasis by mediating FAT4 ubiquitination and degradation |
| title_full_unstemmed | UBE4B promotes gastric cancer proliferation and metastasis by mediating FAT4 ubiquitination and degradation |
| title_short | UBE4B promotes gastric cancer proliferation and metastasis by mediating FAT4 ubiquitination and degradation |
| title_sort | ube4b promotes gastric cancer proliferation and metastasis by mediating fat4 ubiquitination and degradation |
| url | https://doi.org/10.1038/s41419-025-07794-8 |
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