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儿茶素通过依赖于 syntaxin binding protein 1(STXBP1)抑制巨噬细胞浸润和 CD47 介导的免疫逃逸来抑制头颈部鳞状细胞癌(HNSC)。

Catechin suppresses HNSC via STXBP1 dependent inhibition of macrophage infiltration and CD47 mediated immune evasion.

作者信息

Hao Ling, Ma Shuang, Yu Yang, Zhang Baitao

机构信息

Department of Otolaryngology, The Affiliated Hospital of Changchun, University of Chinese Medicine, Changchun, China.

Department of Otolaryngology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Hongkou District, Shanghai, 200437, China.

出版信息

Sci Rep. 2025 Jul 4;15(1):23968. doi: 10.1038/s41598-025-07855-0.

Abstract

The treatment of head and neck squamous cell carcinoma (HNSC) faces significant challenges, primarily due to the lack of reliable biomarkers and effective therapeutic drugs. This study reveals the crucial mechanistic role of STXBP1 in the HNSC tumor microenvironment: STXBP1 promotes tumor immune escape through dual pathways, not only enhancing the infiltration of M2-type macrophages but also activating the 'don't eat me' signaling pathway through upregulation of CD47. Clinical data analysis demonstrates that STXBP1 expression levels significantly correlate with HNSC patient prognosis, suggesting its potential as a diagnostic marker and prognostic indicator. Mechanistic studies show that targeted inhibition of STXBP1 effectively downregulates CD47 expression and restores the anti-tumor function of macrophages. Based on bioinformatics screening and experimental validation, we discovered that the natural compound Catechin can specifically inhibit STXBP1 expression and significantly suppress tumor growth. These findings not only elucidate the molecular mechanism of STXBP1 in HNSC but also provide a new candidate drug for clinical treatment, holding significant translational medical value.

摘要

头颈部鳞状细胞癌(HNSC)的治疗面临重大挑战,主要原因是缺乏可靠的生物标志物和有效的治疗药物。本研究揭示了STXBP1在HNSC肿瘤微环境中的关键机制作用:STXBP1通过双重途径促进肿瘤免疫逃逸,不仅增强M2型巨噬细胞的浸润,还通过上调CD47激活“别吃我”信号通路。临床数据分析表明,STXBP1表达水平与HNSC患者预后显著相关,提示其作为诊断标志物和预后指标的潜力。机制研究表明,靶向抑制STXBP1可有效下调CD47表达并恢复巨噬细胞的抗肿瘤功能。基于生物信息学筛选和实验验证,我们发现天然化合物儿茶素可特异性抑制STXBP1表达并显著抑制肿瘤生长。这些发现不仅阐明了STXBP1在HNSC中的分子机制,还为临床治疗提供了一种新的候选药物,具有重要的转化医学价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d262/12227743/e8093bf173d9/41598_2025_7855_Fig1_HTML.jpg

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