Liu Zhihan, Lei Meng, Bai Yanxia
Department of Otorhinolaryngology-Head & Neck Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
J Inflamm Res. 2025 Jan 22;18:1067-1090. doi: 10.2147/JIR.S485159. eCollection 2025.
Prolonged psychological stress is closely associated with cancer due to its role in promoting the release of stress hormones through the sustained activation of the sympathetic-adrenal-medullary system. These hormones interact with receptors on inflammatory cells, leading to the activation of key signaling pathways, including the transcription factors signal transducer and activator of transcription 3 (STAT-3) and kappa-light-chain-enhancer of activated B cells (NF-κB). These factors drive the production of pro-inflammatory substances, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which can influence the initiation and progression of cancer.
This article aims to summarize how the chronic inflammatory environment induced by chronic stress promotes the initiation, progression, and invasion of cancer. By enhancing our understanding of the complex mechanisms through which stress contributes to cancer, we hope to identify new targets for cancer prevention and treatment.
Chronic stress establishes an inflammatory microenvironment by activating STAT-3 and NF-κB in inflammatory cells. This ongoing inflammation further enhances the activity of these transcription factors, which serve multiple roles: they act as pro-inflammatory agents in inflammatory cells, maintaining chronic inflammation; as oncogenic transcription factors in premalignant cells, promoting cancer initiation; and as pro-differentiation transcription factors in tumor-infiltrating immune cells, facilitating cancer progression. Additionally, the impact of chronic stress varies among different cancer types and individual responses to stress, highlighting the complexity of stress-related cancer mechanisms. Ultimately, this dynamic interplay creates a feedback loop involving IL-6, STAT-3, and TNF-α-NF-κB within the tumor microenvironment, mediating the intricate interactions between inflammation, immunity, and cancer.
长期心理压力与癌症密切相关，因为它通过持续激活交感-肾上腺-髓质系统促进应激激素的释放。这些激素与炎症细胞上的受体相互作用，导致关键信号通路的激活，包括转录因子信号转导和转录激活因子3（STAT-3）以及活化B细胞的κ轻链增强子（NF-κB）。这些因子驱动促炎物质的产生，如白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α），它们可影响癌症的发生和发展。
本文旨在总结慢性应激诱导的慢性炎症环境如何促进癌症的发生、发展和侵袭。通过加深我们对压力导致癌症的复杂机制的理解，我们希望确定癌症预防和治疗的新靶点。
慢性应激通过激活炎症细胞中的STAT-3和NF-κB建立炎症微环境。这种持续的炎症进一步增强了这些转录因子的活性，这些转录因子发挥多种作用：它们在炎症细胞中作为促炎剂，维持慢性炎症；在癌前细胞中作为致癌转录因子，促进癌症发生；在肿瘤浸润免疫细胞中作为促分化转录因子，促进癌症进展。此外，慢性应激的影响在不同癌症类型和个体对压力的反应中有所不同，突出了应激相关癌症机制的复杂性。最终，这种动态相互作用在肿瘤微环境中形成了一个涉及IL-6、STAT-3和TNF-α-NF-κB的反馈回路，介导炎症、免疫和癌症之间的复杂相互作用。
