N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells
Abstract Castration-resistance of prostate cancer is one of the most challenging clinical problems. In the present study, we have performed proteomics and glycomics using LNCaP model. Growth differentiation factor-15 (GDF15) level is increased in androgen receptor (AR) inhibitor-resistant cells and...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-07-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05090-3 |
| _version_ | 1811287423650365440 |
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| author | Rong Wang Piaopiao Wen Ganglong Yang Yanyan Feng Yuanyuan Mi Xiaoying Wang Shenglong Zhu Yong Q. Chen |
| author_facet | Rong Wang Piaopiao Wen Ganglong Yang Yanyan Feng Yuanyuan Mi Xiaoying Wang Shenglong Zhu Yong Q. Chen |
| author_sort | Rong Wang |
| collection | DOAJ |
| description | Abstract Castration-resistance of prostate cancer is one of the most challenging clinical problems. In the present study, we have performed proteomics and glycomics using LNCaP model. Growth differentiation factor-15 (GDF15) level is increased in androgen receptor (AR) inhibitor-resistant cells and the inhibitory effect of GDF15 on epithelial growth factor receptor (EGFR) pathway is relieved by GDF15 N70 glycosylation. Interference of GDF15 (siRNA or N70Q dominant negative) or EGFR pathway (inhibitor or siRNA for EGFR, SRC or ERK) decreases the resistant-cell survival in culture and tumor growth in mice. Our study reveals a novel regulatory mechanism of prostate cancer AR inhibitor resistance, raises the possibility of AR/SRC dual-targeting of castration-resistance of prostate cancer, and lays foundation for the future development of selective inhibitors of GDF15 glycosylation. |
| first_indexed | 2024-04-13T03:18:11Z |
| format | Article |
| id | doaj.art-1d43ac75d1f048a9a32a5eb02b52bd97 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-13T03:18:11Z |
| publishDate | 2022-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-1d43ac75d1f048a9a32a5eb02b52bd972022-12-22T03:04:50ZengNature Publishing GroupCell Death and Disease2041-48892022-07-0113711210.1038/s41419-022-05090-3N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cellsRong Wang0Piaopiao Wen1Ganglong Yang2Yanyan Feng3Yuanyuan Mi4Xiaoying Wang5Shenglong Zhu6Yong Q. Chen7Wuxi School of Medicine, Jiangnan UniversitySchool of Biological Engineering, Jiangnan UniversitySchool of Biological Engineering, Jiangnan UniversityWuxi School of Medicine, Jiangnan UniversityDepartment of Urology, Affiliated Hospital of Jiangnan UniversityWuxi School of Medicine, Jiangnan UniversityWuxi School of Medicine, Jiangnan UniversityWuxi School of Medicine, Jiangnan UniversityAbstract Castration-resistance of prostate cancer is one of the most challenging clinical problems. In the present study, we have performed proteomics and glycomics using LNCaP model. Growth differentiation factor-15 (GDF15) level is increased in androgen receptor (AR) inhibitor-resistant cells and the inhibitory effect of GDF15 on epithelial growth factor receptor (EGFR) pathway is relieved by GDF15 N70 glycosylation. Interference of GDF15 (siRNA or N70Q dominant negative) or EGFR pathway (inhibitor or siRNA for EGFR, SRC or ERK) decreases the resistant-cell survival in culture and tumor growth in mice. Our study reveals a novel regulatory mechanism of prostate cancer AR inhibitor resistance, raises the possibility of AR/SRC dual-targeting of castration-resistance of prostate cancer, and lays foundation for the future development of selective inhibitors of GDF15 glycosylation.https://doi.org/10.1038/s41419-022-05090-3 |
| spellingShingle | Rong Wang Piaopiao Wen Ganglong Yang Yanyan Feng Yuanyuan Mi Xiaoying Wang Shenglong Zhu Yong Q. Chen N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells Cell Death and Disease |
| title | N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells |
| title_full | N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells |
| title_fullStr | N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells |
| title_full_unstemmed | N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells |
| title_short | N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells |
| title_sort | n glycosylation of gdf15 abolishes its inhibitory effect on egfr in ar inhibitor resistant prostate cancer cells |
| url | https://doi.org/10.1038/s41419-022-05090-3 |
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