结直肠癌中微生物- tlr4信号轴的多维调控:从分子机制到微生物靶向治疗

IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Caihou Zhang , Haimin Geng , Yurong Tan , Lili Wang
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引用次数: 0

摘要

结直肠癌(CRC)是全球第三大常见癌症,是遗传易感性、环境因素和肠道菌群失调之间复杂相互作用的结果。本文系统分析了CRC中微生物-TLR4信号轴的多角度调控机制,包括TLR4/NF-κB、MAPK、TRIF/IRF3、Keap1/NRF2/CYP2J2、神经酰胺/β-catenin/SOAT1等关键通路。这些途径通过代谢重编程、免疫调节和基因毒性作用驱动肿瘤进展。针对这一轴的治疗策略包括天然化合物(如萜类、多糖、皂苷)、中药方剂(如甘露饮、小菜护汤)、微生物群疗法(益生菌、工程菌、溶瘤病毒)以及饮食和代谢调节(膳食纤维、蛋氨酸),通过抑制TLR4过度激活、修复肠道屏障、调节微生物平衡来发挥抗肿瘤作用。该综述强调了诸如信号通路的复杂性、精确的微生物群调节和药物递送等挑战。与此同时,单细胞多组学和人工智能预测模型等新兴技术为精准干预提供了新的方向。靶向微生物- tlr4轴有望成为CRC治疗的一种创新策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Multidimensional regulation of the microbe-TLR4 signaling Axis in colorectal cancer: From molecular mechanisms to microbe-targeted therapies
Colorectal cancer (CRC), the third most common cancer globally, arises from complex interactions between genetic predisposition, environmental factors, and gut microbiota dysbiosis. This review systematically analyzes the multidimensional regulatory mechanisms of the microbe-TLR4 signaling axis in CRC, including key pathways such as TLR4/NF-κB, MAPK, TRIF/IRF3, Keap1/NRF2/CYP2J2, and ceramide/β-catenin/SOAT1. These pathways drive tumor progression through metabolic reprogramming, immune modulation, and genotoxic effects. Therapeutic strategies targeting this axis encompass natural compounds (e.g., terpenoids, polysaccharides, saponins), traditional Chinese medicine formulas (e.g., Ganluyin, Xiao-Chai-Hu-Tang), microbiota therapies (probiotics, engineered bacteria, oncolytic viruses), and dietary and metabolic regulation (dietary fiber, methionine), exerting anti-tumor effects by inhibiting excessive TLR4 activation, repairing intestinal barriers, and regulating microbial balance. The review highlights challenges such as the complexity of signaling pathways, precise microbiota modulation, and drug delivery. At the same time, emerging technologies like single-cell multi-omics and artificial intelligence prediction models offer new directions for precision interventions. Targeting the microbe-TLR4 axis holds promise as an innovative strategy for CRC treatment.
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来源期刊
Biochimica et biophysica acta. Reviews on cancer
Biochimica et biophysica acta. Reviews on cancer 医学-生化与分子生物学
CiteScore
17.20
自引率
0.00%
发文量
138
审稿时长
33 days
期刊介绍: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer encompasses the entirety of cancer biology and biochemistry, emphasizing oncogenes and tumor suppressor genes, growth-related cell cycle control signaling, carcinogenesis mechanisms, cell transformation, immunologic control mechanisms, genetics of human (mammalian) cancer, control of cell proliferation, genetic and molecular control of organismic development, rational anti-tumor drug design. It publishes mini-reviews and full reviews.
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