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Psychological stress-activated NR3C1/NUPR1 axis promotes ovarian tumor metastasis

2025-07-09
(Press-News.org) https://doi.org/10.1016/j.apsb.2025.04.001

This new article publication from Acta Pharmaceutica Sinica B, discusses how a psychological stress-activated NR3C1/NUPR1 axis promotes ovarian tumor metastasis.

 

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.

 

The authors of this article 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, this 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.

 

Keywords: NR3C1, NUPR1, Ovarian tumor, EMT, Prognostic biomarker, Psychological stress, Therapeutic target, SNAI2

 

Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S2211383525002187-ga1_lrg.jpg

Psychological stress-induced NR3C1 activation promotes NUPR1 transcription, thereby evoking ovarian tumor (OT) metastasis. It highlights the potential of targeting the NR3C1–NUPR1 axis as a therapeutic strategy for treating stress-exacerbated OT.

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The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association.

For more information please visit https://www.journals.elsevier.com/acta-pharmaceutica-sinica-b/

Editorial Board: https://www.journals.elsevier.com/acta-pharmaceutica-sinica-b/editorial-board

 

APSB is available on ScienceDirect (https://www.sciencedirect.com/journal/acta-pharmaceutica-sinica-b).

 

Submissions to APSB may be made using Editorial Manager® (https://www.editorialmanager.com/apsb/default.aspx).

 

CiteScore: 24.3

Impact Factor: 14.6 (Top 6 journal in the category of Pharmacology and pharmacy) 

JIF without self-citation: 13.8

ISSN 2211-3835

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Bin Liu, Wen-Zhe Deng, Wen-Hua Hu, Rong-Xi Lu, Qing-Yu Zhang, Chen-Feng Gao, Xiao-Jie Huang, Wei-Guo Liao, Jin Gao, Yang Liu, Hiroshi Kurihara, Yi-Fang Li, Xu-Hui Zhang, Yan-Ping Wu, Lei Liang, Rong-Rong He, Psychological stress-activated NR3C1/NUPR1 axis promotes ovarian tumor metastasis, Acta Pharmaceutica Sinica B, Volume 15, Issue 6, 2025, Pages 3149-3162, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2025.04.001

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[Press-News.org] Psychological stress-activated NR3C1/NUPR1 axis promotes ovarian tumor metastasis