SIRT7 facilitates endometrial cancer progression by regulating PTEN stability in an estrogen-dependent manner

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 () and Xiaoping Wan ()
Additional contact information
Zhiyi Hu: Tongji University
Ming Tang: Tongji University
Yujia Huang: Tongji University
Bailian Cai: Tongji University
Xiaoxiang Sun: Tongji University
Guofang Chen: Tongji University
Ao Huang: Changsha Medical University
Xiaoqi Li: University of Nebraska Medical Center
Ab Rauf Shah: University of Nebraska Medical Center
Lijun Jiang: Tongji University
Qian Li: Tongji University
Xianghong Xu: Tongji University
Wen Lu: Tongji University
Zhiyong Mao: Tongji University
Xiaoping Wan: Tongji University

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-58317-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58317-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-58317-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().