EDA2R-NIK signaling in cancer cachexia.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-09-01 Epub Date: 2024-05-27 DOI:10.1097/SPC.0000000000000705

Samet Agca, Serkan Kir

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引用次数: 0

Abstract

Purpose of review: Cachexia is a debilitating condition causing weight loss and skeletal muscle wasting that negatively influences treatment and survival of cancer patients. The objective of this review is to describe recent discoveries on the role of a novel signaling pathway involving ectodysplasin A2 receptor (EDA2R) and nuclear factor κB (NFκB)-inducing kinase (NIK) in muscle atrophy.

Recent findings: Studies identified tumor-induced upregulation of EDA2R expression in muscle tissues in pre-clinical cachexia models and patients with various cancers. Activation of EDA2R by its ligand promoted atrophy in cultured myotubes and muscle tissue, which depended on NIK activity. The non-canonical NFκB pathway via NIK also stimulated muscle atrophy. Mice lacking EDA2R or NIK were protected from muscle loss due to tumors. Tumor-induced cytokine oncostatin M (OSM) upregulated EDA2R expression in muscles whereas OSM receptor-deficient mice were resistant to muscle wasting.

Summary: Recent discoveries revealed a mechanism involving EDA2R-NIK signaling and OSM that drives cancer-associated muscle loss, opening up new directions for designing anti-cachexia treatments. The therapeutic potential of targeting this mechanism to prevent muscle loss should be further investigated. Future research should also explore broader implications of the EDA2R-NIK pathway in other muscle wasting diseases and overall muscle health.

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癌症恶病质中的 EDA2R-NIK 信号转导

审查目的：恶病质是一种导致体重减轻和骨骼肌萎缩的衰弱病症，对癌症患者的治疗和生存产生负面影响。本综述旨在描述最近发现的涉及外胚层蛋白 A2 受体（EDA2R）和核因子κB（NFκB）诱导激酶（NIK）的新型信号通路在肌肉萎缩中的作用：研究发现，在临床前恶病质模型和各种癌症患者的肌肉组织中，肿瘤诱导 EDA2R 表达上调。EDA2R的配体激活促进了培养肌管和肌肉组织的萎缩，而这取决于NIK的活性。通过 NIK 的非经典 NFκB 通路也会刺激肌肉萎缩。缺乏 EDA2R 或 NIK 的小鼠不会因肿瘤而导致肌肉萎缩。肿瘤诱导的细胞因子oncostatin M（OSM）会上调肌肉中EDA2R的表达，而OSM受体缺乏的小鼠对肌肉萎缩有抵抗力：最近的发现揭示了一种涉及EDA2R-NIK信号转导和OSM的机制，该机制驱动癌症相关性肌肉萎缩，为设计抗痛风治疗方法开辟了新方向。针对这一机制预防肌肉萎缩的治疗潜力有待进一步研究。未来的研究还应探索 EDA2R-NIK 通路对其他肌肉萎缩疾病和整体肌肉健康的广泛影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.