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

Bin Liu1,2,3, Wen-Zhe Deng2,3,4, Wen-Hua Hu5

  • 1Laboratory of Hepatobiliary Surgery, Zhanjiang Key Laboratory of Hepatobiliary Related Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.

Acta Pharmaceutica Sinica. B
|July 14, 2025
PubMed

Insights

Psychological stress accelerates ovarian tumor metastasis via the glucocorticoid receptor (NR3C1) and nuclear protein 1 (NUPR1) pathway. This NR3C1/NUPR1 axis promotes cancer spread and is linked to poorer patient prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Stress Physiology

Background:

  • Ovarian tumors (OT) are highly lethal gynecologic malignancies with poor patient outcomes.
  • Metastasis is the primary cause of OT-related deaths, with poorly understood mechanisms.
  • Psychological stress activates the glucocorticoid receptor (NR3C1), linked to poor OT prognosis.

Purpose of the Study:

  • To elucidate the mechanisms linking NR3C1 signaling and ovarian tumor metastasis under psychological stress.
  • To identify key molecular players in stress-induced ovarian cancer progression.

Main Methods:

  • Investigated the role of NR3C1 and NUPR1 in stress-induced OT metastasis.
  • Analyzed NR3C1's regulation of NUPR1 transcription and its downstream effects on EMT drivers like SNAI2.
  • Correlated NR3C1 and NUPR1 expression with clinical prognosis in OT patients.

Main Results:

  • Chronic restraint stress accelerated OT epithelial-mesenchymal transition (EMT) and metastasis via an NR3C1-dependent pathway involving NUPR1.
  • NR3C1 directly upregulated NUPR1 transcription, increasing SNAI2 expression, a key EMT driver.
  • Elevated NR3C1 and NUPR1 levels in patients correlated with poorer OT prognosis.

Conclusions:

  • Identified the NR3C1/NUPR1 axis as a critical regulator of psychological stress-induced OT metastasis.
  • The NR3C1/NUPR1 pathway represents a potential therapeutic target for mitigating ovarian cancer spread.
Keywords:
EMTNR3C1NUPR1Ovarian tumorPrognostic biomarkerPsychological stressSNAI2Therapeutic target

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