Research progress on chronic stress stimulation and gastric cancer metastasis

Gastric cancer remains a major clinical challenge due to its propensity for metastasis and poor five-year survival rates. Emerging evidence implicates chronic psychological stress as a critical promoter of tumor dissemination. Stress signals engage both the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), leading to sustained elevations of cortisol and catecholamines. These mediators act on glucocorticoid receptors (GR) and β-adrenergic receptors (ADRB2) in gastric cancer cells, thereby activating downstream cAMP/PKA and NF-κB/STAT3 pathways. The resulting cascade enhances epithelial-mesenchymal transition (EMT), upregulates matrix metalloproteinases, and promotes neovascularization, while concurrently inducing an immunosuppressive microenvironment characterized by CD8⁺ T-cell exhaustion, M2-polarized TAMs, and Treg expansion. Moreover, stress-driven epigenetic and metabolic reprogramming amplifies the Warburg effect and synergizes with Helicobacter pylori infection to accelerate tumor invasion. Clinical and cohort studies consistently associate elevated stress markers with increased metastasis risk, and interventions-ranging from β-blockers and GR antagonists to cognitive-behavioral therapy-show promise in mitigating these effects. Future advances in multi-omics, spatial profiling, smart probiotics, and optogenetic tools are poised to unravel the complex "stress-tumor" interface and enable precise, integrative mind-body therapeutic strategies.