REVIEW article
Front. Oncol.
Sec. Cancer Cell Signaling
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1682238
Chronic Stress-Driven Tumor Metastasis: Exploring the Gut-Brain Axis
Provisionally accepted
- 1Shandong University of Traditional Chinese Medicine, Jinan, China
- 2Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
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Word count: 146 Metastasis, the leading cause of death in patients with solid tumors, involves the spread of cancer cells to distant organs. While genetic and environmental factors contribute, chronic stress is a crucial factor in metastatic progression by disrupting neuroendocrine, immune, metabolic, and microbial homeostasis. This review synthesizes evidence linking chronic stress to tumor metastasis through three pathways: (1) direct effects on tumor cell metabolism, (2) remodeling of the tumor microenvironment, and (3) dysregulation of the gut microbiota. Describe how activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system influences epithelial-mesenchymal transition, immune evasion, and angiogenesis via β-adrenergic and glucocorticoid receptor signaling. Explore how microbial metabolites and barrier dysfunction influence immune and neuroendocrine circuits, creating a pro-metastatic loop. Finally, we highlight therapeutic strategies, including psychological interventions and pharmacologic approaches, to alleviate chronic stress. This review proposes a mechanistic framework linking neuroendocrine signaling, metabolic reprogramming, and the microbiome-immune axis.
Keywords: chronic stress, Tumor metastasis, Neuroendocrine regulation, Tumor Microenvironment, Gut Microbiota, metabolic reprogramming
Received: 08 Aug 2025; Accepted: 29 Sep 2025.
Copyright: © 2025 Wang, Sun, Li, Xu and Cui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wenqiang Cui, wqcui16@fudan.edu.cn
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