慢性压力通过肾上腺素受体β2/PlexinA1途径促进胃癌进展

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Yanjie Lu , Die Cheng , Jiayu Pang , Yuqiao Peng , Shunkang Jin , Xinyu Zhang , Yuhong Li , Yanzhen Zuo
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引用次数: 0

摘要

背景:慢性压力是癌症患者常见的情绪障碍。慢性应激会促进胃癌(GC)的进展并导致不良预后。然而,其潜在机制仍不清楚。在此,我们探讨了慢性应激在胃癌进展中的可能机制:方法:分析 TCGA 数据集,寻找差异表达基因。使用癌症基因组图谱(TCGA)和Kaplan-Meier(KM)-plotter数据库评估GC临床数据与PlexinA1的关联。使用焦虑自评量表和抑郁自评量表评估了癌症患者的慢性压力。慢性不可预测轻度应激(CUMS)用于诱导小鼠的慢性应激。采用缝合法构建胃异种移植瘤。使用光/暗箱和尾悬试验评估慢性应激样行为。使用免疫组化和Western印迹分析检测蛋白质表达:结果:对TCGA和KM-plotter数据库的分析表明,与PlexinA1水平低的患者相比,PlexinA1水平高的GC患者总生存期更短。共有36名癌症患者参与了这项研究,其中约33%的患者有慢性压力。与无慢性压力的患者相比,慢性压力患者肾上腺素受体β2(ADRB2)和PlexinA1的表达水平更高。与对照组小鼠相比,接受CUMS治疗的小鼠肿瘤体积明显增大。ADRB2、PlexinA1、N-cadherin、α-平滑肌肌动蛋白(α-SMA)和 Ki67 在 CUMS 组肿瘤中高表达。然而,E-cadherin在CUMS组肿瘤中表达较低。重要的是,用6-羟基多巴胺(6-OHDA)进行化学交感神经切除术或用选择性β2肾上腺素能受体拮抗剂(ICI118,551)治疗可逆转这些影响:我们的研究结果表明,慢性应激在 GC 的发展过程中起着重要作用,阻断肾上腺素-β2AR/PlexinA1 通路有可能治疗 GC。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Chronic stress promotes gastric cancer progression via the adrenoceptor beta 2/PlexinA1 pathway

Chronic stress promotes gastric cancer progression via the adrenoceptor beta 2/PlexinA1 pathway

Chronic stress is a common emotional disorder in cancer patients. Chronic stress promotes progression of gastric cancer (GC) and leads to poor outcomes. However, the underlying mechanisms remain not clear. Herein, we explored the possible mechanisms of chronic stress in GC progression. The Cancer Genome Atlas (TCGA) datasets were analyzed for differentially expressed genes. Clinical data of GC were evaluated for their association with PlexinA1 using TCGA and Kaplan–Meier-plotter databases. Chronic stress of GC patients was evaluated using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Chronic unpredictable mild stress (CUMS) was used to induce chronic stress in mice. Gastric xenograft tumor was constructed using the sewing method. Chronic stress-like behaviors were assessed using light/dark box and tail suspension tests. Protein expression was detected using immunohistochemistry and Western blot analysis. Analyses of TCGA and the Kaplan–Meier-plotter databases showed that patients with high levels of PlexinA1 in GC had worse overall survival than those with low levels of PlexinA1. A total of 36 GC patients were enrolled in the study, and about 33% of the patients had chronic stress. Compared with patients without chronic stress, higher expression levels of adrenoceptor beta 2 and PlexinA1 were observed in patients with chronic stress. The tumor size in mice under CUMS was significantly increased compared with the control mice. Adrenoceptor beta 2, PlexinA1, N-cadherin, and alpha-smooth muscle actin, as well as Ki67 were highly expressed in the tumors of CUMS group. However, E-cadherin was lowly expressed in the tumors of CUMS group. Importantly, chemical sympathectomy with 6-hydroxydopamine or treatment with a selective β2 adrenergic receptor antagonist (ICI118,551) could reverse these effects. Our findings suggest that chronic stress plays an important role in GC progression and there is a potential for blocking the epinephrine-β2AR/PlexinA1 pathway in the treatment of GC.

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来源期刊
Cell Stress & Chaperones
Cell Stress & Chaperones 生物-细胞生物学
CiteScore
7.60
自引率
2.60%
发文量
59
审稿时长
6-12 weeks
期刊介绍: Cell Stress and Chaperones is an integrative journal that bridges the gap between laboratory model systems and natural populations. The journal captures the eclectic spirit of the cellular stress response field in a single, concentrated source of current information. Major emphasis is placed on the effects of climate change on individual species in the natural environment and their capacity to adapt. This emphasis expands our focus on stress biology and medicine by linking climate change effects to research on cellular stress responses of animals, micro-organisms and plants.
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