SIRT7 facilitates endometrial cancer progression by regulating PTEN stability in an estrogen-dependent manner
Abstract The prognosis of metastatic endometrial carcinoma (EC), one of the most common gynecological malignancies worldwide, remains poor, and the underlying driver of metastases is poorly understood. Dysregulation in estrogen-related signaling and inactivation of tumor suppressor PTEN are two esse...
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58317-0 |
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| author | Zhiyi Hu Ming Tang Yujia Huang Bailian Cai Xiaoxiang Sun Guofang Chen Ao Huang Xiaoqi Li Ab Rauf Shah Lijun Jiang Qian Li Xianghong Xu Wen Lu Zhiyong Mao Xiaoping Wan |
| author_facet | Zhiyi Hu Ming Tang Yujia Huang Bailian Cai Xiaoxiang Sun Guofang Chen Ao Huang Xiaoqi Li Ab Rauf Shah Lijun Jiang Qian Li Xianghong Xu Wen Lu Zhiyong Mao Xiaoping Wan |
| author_sort | Zhiyi Hu |
| collection | DOAJ |
| description | Abstract The prognosis of metastatic endometrial carcinoma (EC), one of the most common gynecological malignancies worldwide, remains poor, and the underlying driver of metastases is poorly understood. Dysregulation in estrogen-related signaling and inactivation of tumor suppressor PTEN are two essential risk factors of EC. However, whether and how they are interconnected during EC development remains unclear. Here, we demonstrate that the deacetylase SIRT7 is upregulated in EC patients and mouse models, facilitating EC progression in vitro and in vivo. Mechanistically, in an estrogen-dependent fashion, SIRT7 mediates PTEN deacetylation at K260, promoting PTEN ubiquitination by the E3 ligase NEDD4L, accelerating PTEN degradation and, consequently, expediting EC metastasis. Additionally, SIRT7 expression strongly correlates with poor survival in EC patients with wild-type PTEN, though no significant correlation is observed in PTEN mutation patients. These results lay the foundation for the study of targeting estrogen-SIRT7-PTEN axis, to restore PTEN abundance, offering potential avenues for EC therapy. |
| format | Article |
| id | doaj-art-151f4bdc2d7e4698b2cf0c48c352ccaf |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-151f4bdc2d7e4698b2cf0c48c352ccaf2025-08-20T02:10:14ZengNature PortfolioNature Communications2041-17232025-03-0116112010.1038/s41467-025-58317-0SIRT7 facilitates endometrial cancer progression by regulating PTEN stability in an estrogen-dependent mannerZhiyi Hu0Ming Tang1Yujia Huang2Bailian Cai3Xiaoxiang Sun4Guofang Chen5Ao Huang6Xiaoqi Li7Ab Rauf Shah8Lijun Jiang9Qian Li10Xianghong Xu11Wen Lu12Zhiyong Mao13Xiaoping Wan14Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityShanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityShanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityHunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, School of Pharmacy, Changsha Medical UniversityDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical CenterDepartment of Pathology and Microbiology, University of Nebraska Medical CenterShanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityShanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityShanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityShanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji UniversityAbstract The prognosis of metastatic endometrial carcinoma (EC), one of the most common gynecological malignancies worldwide, remains poor, and the underlying driver of metastases is poorly understood. Dysregulation in estrogen-related signaling and inactivation of tumor suppressor PTEN are two essential risk factors of EC. However, whether and how they are interconnected during EC development remains unclear. Here, we demonstrate that the deacetylase SIRT7 is upregulated in EC patients and mouse models, facilitating EC progression in vitro and in vivo. Mechanistically, in an estrogen-dependent fashion, SIRT7 mediates PTEN deacetylation at K260, promoting PTEN ubiquitination by the E3 ligase NEDD4L, accelerating PTEN degradation and, consequently, expediting EC metastasis. Additionally, SIRT7 expression strongly correlates with poor survival in EC patients with wild-type PTEN, though no significant correlation is observed in PTEN mutation patients. These results lay the foundation for the study of targeting estrogen-SIRT7-PTEN axis, to restore PTEN abundance, offering potential avenues for EC therapy.https://doi.org/10.1038/s41467-025-58317-0 |
| spellingShingle | Zhiyi Hu Ming Tang Yujia Huang Bailian Cai Xiaoxiang Sun Guofang Chen Ao Huang Xiaoqi Li Ab Rauf Shah Lijun Jiang Qian Li Xianghong Xu Wen Lu Zhiyong Mao Xiaoping Wan SIRT7 facilitates endometrial cancer progression by regulating PTEN stability in an estrogen-dependent manner Nature Communications |
| title | SIRT7 facilitates endometrial cancer progression by regulating PTEN stability in an estrogen-dependent manner |
| title_full | SIRT7 facilitates endometrial cancer progression by regulating PTEN stability in an estrogen-dependent manner |
| title_fullStr | SIRT7 facilitates endometrial cancer progression by regulating PTEN stability in an estrogen-dependent manner |
| title_full_unstemmed | SIRT7 facilitates endometrial cancer progression by regulating PTEN stability in an estrogen-dependent manner |
| title_short | SIRT7 facilitates endometrial cancer progression by regulating PTEN stability in an estrogen-dependent manner |
| title_sort | sirt7 facilitates endometrial cancer progression by regulating pten stability in an estrogen dependent manner |
| url | https://doi.org/10.1038/s41467-025-58317-0 |
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