Psychological stress-activated NR3C1/NUPR1 axis promotes ovarian tumor metastasis.
10.1016/j.apsb.2025.04.001
- Author:
Bin LIU
1
;
Wen-Zhe DENG
2
;
Wen-Hua HU
3
;
Rong-Xi LU
3
;
Qing-Yu ZHANG
4
;
Chen-Feng GAO
1
;
Xiao-Jie HUANG
1
;
Wei-Guo LIAO
3
;
Jin GAO
5
;
Yang LIU
2
;
Hiroshi KURIHARA
2
;
Yi-Fang LI
2
;
Xu-Hui ZHANG
6
;
Yan-Ping WU
2
;
Lei LIANG
2
;
Rong-Rong HE
2
Author Information
1. Laboratory of Hepatobiliary Surgery, Zhanjiang Key Laboratory of Hepatobiliary Related Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
2. State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility, Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products, International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, China.
3. Pathology Diagnosis and Research Center, the Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
4. Laboratory of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, the Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
5. College of Pharmacy, Jinan University, Guangzhou 510632, China.
6. Department of Oncology, Guangdong Second Provincial General Hospital, the Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou 510317, China.
- Publication Type:Journal Article
- Keywords:
EMT;
NR3C1;
NUPR1;
Ovarian tumor;
Prognostic biomarker;
Psychological stress;
SNAI2;
Therapeutic target
- From:
Acta Pharmaceutica Sinica B
2025;15(6):3149-3162
- CountryChina
- Language:English
-
Abstract:
Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.
