恶病质是一种使人衰弱的疾病，会导致体重减轻和骨骼肌萎缩，对癌症患者的治疗和生存产生负面影响。本综述的目的是描述涉及外胚层增生素 A2 受体 (EDA2R) 和核因子 κB (NFκB) 诱导激酶 (NIK) 在肌肉萎缩中的新信号通路作用的最新发现。研究发现肿瘤诱导的 EDA2R 上调临床前恶病质模型和各种癌症患者肌肉组织中的表达。 EDA2R 的配体激活促进了培养的肌管和肌肉组织的萎缩，这取决于 NIK 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 的小鼠可以免受肿瘤引起的肌肉损失。肿瘤诱导的细胞因子制瘤素 M (OSM) 上调肌肉中的 EDA2R 表达，而 OSM 受体缺陷的小鼠能够抵抗肌肉萎缩。最近的发现揭示了一种涉及 EDA2R-NIK 信号传导和 OSM 的机制，可驱动癌症相关的肌肉损失，开辟了新的方向用于设计抗恶病质治疗。应进一步研究针对这种机制预防肌肉损失的治疗潜力。未来的研究还应探索 EDA2R-NIK 通路在其他肌肉消耗疾病和整体肌肉健康中的更广泛影响。版权所有 © 2024 Wolters Kluwer Health, Inc. 保留所有权利。

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.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.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.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.