GILT stabilizes cofilin to promote the metastasis of prostate cancer
Abstract Gamma-interferon-induced lysosomal thiol reductase (GILT), known for catalyzing disulfide bond reduction, is involved in various physiological processes. While the involvement of GILT in the development of various tumors has been demonstrated, the mechanisms underlying its regulation in pro...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02288-0 |
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| _version_ | 1832594957943177216 |
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| author | Dunsheng Han Zhiming Wu Cong Zhang Ziwei Wei Fan Chao Xuefeng Xie Jinke Liu Yufeng Song Xiaoming Song Dingchang Shao Shiyu Wang Guoxiong Xu Gang Chen |
| author_facet | Dunsheng Han Zhiming Wu Cong Zhang Ziwei Wei Fan Chao Xuefeng Xie Jinke Liu Yufeng Song Xiaoming Song Dingchang Shao Shiyu Wang Guoxiong Xu Gang Chen |
| author_sort | Dunsheng Han |
| collection | DOAJ |
| description | Abstract Gamma-interferon-induced lysosomal thiol reductase (GILT), known for catalyzing disulfide bond reduction, is involved in various physiological processes. While the involvement of GILT in the development of various tumors has been demonstrated, the mechanisms underlying its regulation in prostate cancer (PCa) are not fully understood. In the present study, we confirmed that GILT was significantly upregulated in PCa and facilitated tumor metastasis. Mechanistically, GILT stabilized the cofilin protein by competitively binding to cofilin with Src family tyrosine kinase (SRC), inhibiting SRC-mediated tyrosine phosphorylation of cofilin, thereby suppressing the ubiquitination pathway degradation of cofilin. GILT overexpression stabilized and increased the protein level of cofilin in PCa cells and promoted the metastasis of PCa cells by accelerating actin dynamics through cofilin-mediated actin severing. Our findings reveal a novel mechanism of GILT in PCa and provide a new potential target for the diagnosis and treatment of PCa patients. |
| format | Article |
| id | doaj-art-263b20d18d4a4f14b6e85d0c5dbfdde2 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-263b20d18d4a4f14b6e85d0c5dbfdde22025-01-19T12:10:35ZengNature Publishing GroupCell Death Discovery2058-77162025-01-0111111410.1038/s41420-025-02288-0GILT stabilizes cofilin to promote the metastasis of prostate cancerDunsheng Han0Zhiming Wu1Cong Zhang2Ziwei Wei3Fan Chao4Xuefeng Xie5Jinke Liu6Yufeng Song7Xiaoming Song8Dingchang Shao9Shiyu Wang10Guoxiong Xu11Gang Chen12Department of Urology, Jinshan Hospital, Fudan UniversityDepartment of Urology, Sun Yat-sen University Cancer CenterDepartment of Urology, Jinshan Hospital, Fudan UniversityDepartment of Urology, Jinshan Hospital, Fudan UniversityDepartment of Urology, Zhongshan Hospital, Fudan University (Xiamen Branch)Department of Urology, Jinshan Hospital, Fudan UniversityDepartment of Urology, Jinshan Hospital, Fudan UniversityDepartment of Urology, Jinshan Hospital, Fudan UniversityDepartment of Urology, Jinshan Hospital, Fudan UniversityDepartment of Urology, Jinshan Hospital, Fudan UniversityResearch Center for Clinical Medicine, Jinshan Hospital, Fudan UniversityResearch Center for Clinical Medicine, Jinshan Hospital, Fudan UniversityDepartment of Urology, Jinshan Hospital, Fudan UniversityAbstract Gamma-interferon-induced lysosomal thiol reductase (GILT), known for catalyzing disulfide bond reduction, is involved in various physiological processes. While the involvement of GILT in the development of various tumors has been demonstrated, the mechanisms underlying its regulation in prostate cancer (PCa) are not fully understood. In the present study, we confirmed that GILT was significantly upregulated in PCa and facilitated tumor metastasis. Mechanistically, GILT stabilized the cofilin protein by competitively binding to cofilin with Src family tyrosine kinase (SRC), inhibiting SRC-mediated tyrosine phosphorylation of cofilin, thereby suppressing the ubiquitination pathway degradation of cofilin. GILT overexpression stabilized and increased the protein level of cofilin in PCa cells and promoted the metastasis of PCa cells by accelerating actin dynamics through cofilin-mediated actin severing. Our findings reveal a novel mechanism of GILT in PCa and provide a new potential target for the diagnosis and treatment of PCa patients.https://doi.org/10.1038/s41420-025-02288-0 |
| spellingShingle | Dunsheng Han Zhiming Wu Cong Zhang Ziwei Wei Fan Chao Xuefeng Xie Jinke Liu Yufeng Song Xiaoming Song Dingchang Shao Shiyu Wang Guoxiong Xu Gang Chen GILT stabilizes cofilin to promote the metastasis of prostate cancer Cell Death Discovery |
| title | GILT stabilizes cofilin to promote the metastasis of prostate cancer |
| title_full | GILT stabilizes cofilin to promote the metastasis of prostate cancer |
| title_fullStr | GILT stabilizes cofilin to promote the metastasis of prostate cancer |
| title_full_unstemmed | GILT stabilizes cofilin to promote the metastasis of prostate cancer |
| title_short | GILT stabilizes cofilin to promote the metastasis of prostate cancer |
| title_sort | gilt stabilizes cofilin to promote the metastasis of prostate cancer |
| url | https://doi.org/10.1038/s41420-025-02288-0 |
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