胃癌在世界范围内是第二大癌症死亡原因。流行病学研究表明，心理社会应激能促进肿瘤的发生发展，并显著降低肿瘤患者的5年生存率，但其作用机制尚不明了。本课题组前期首次在两种小鼠模型中发现慢性应激可显著促进胃癌的进展，且肿瘤微环境中交感神经释放的去甲肾上腺素对胃癌的进展具有重要作用。进一步通过基因表达谱测序发现，MUC4与ADRB2之间的正反馈作用可能介导了慢性应激促进胃癌进展的过程。根据前期结果，我们提出假说：慢性应激通过激活β2-肾上腺素受体及其下游PKA-CREB/STAT3通路，上调MUC4转录水平，进而通过MUC4活化的Wnt/β-catenin通路促进胃癌的恶性生物学行为；同时，高表达的MUC4可与ADRB2相互作用，形成正反馈机制，进一步放大上述信号传导过程。本项目将运用最新分子生物学技术及生物信息学工具，以期揭示慢性应激在胃癌进展过程中的作用及机制，为胃癌的预防和治疗提供新的思路。

Gastric cancer is the second most frequent cause of cancer-related death worldwide. It is confirmed by epidemiologic studies that psychological stress can contribute to the incidence and progression of cancer, as well as impact the 5-year survival rate. However, the underlying mechanism is still unclear. Our previous work revealed that chronic stress could significantly promote the progression of gastric cancer by two mice models. Norepinephrine released by sympathetic nerve was found to play an important role in gastric cancer progression. With further gene sequencing test and bioinformatic analysis, we found that the positive feedback relationship between MUC4 and ADRB2 was involved. According to the previous foundation, we hypothesize that chronic stress activated the sympathetic nerve system and β2 adrenergic receptor, which leaded to the upregulation of MUC4 transcription. Meanwhile, MUC4 interacted with ADRB2, which further formed a positive feedback relationship to amplify the process above. This study will focus on the effect and underlying mechanism of chronic stress on gastric cancer progression with bioinformatics and molecular techniques, which will provide a new way for gastric cancer prevention and therapy.