Skeletal muscle has long been recognized as an inhospitable site for disseminated tumour cells (DTCs). Yet its antimetastatic nature has eluded a thorough mechanistic examination. Here, we show that DTCs traffic to and persist within skeletal muscle in mice and in humans, which raises the question of how this tissue suppresses colonization. Results from mouse and organotypic culture models along with metabolomic profiling suggested that skeletal muscle imposes a sustained oxidative stress on DTCs that impairs their proliferation. Functional studies demonstrated that disrupting reduction–oxidation homeostasis via chemogenetic induction of reactive oxygen species slowed proliferation in a more fertile organ: the lung. Conversely, enhancement of the antioxidant potential of tumour cells through ectopic expression of catalase in the tumour or host mitochondria allowed robust colonization of skeletal muscle. These findings reveal a profound metabolic bottleneck imposed on DTCs and sustained by skeletal muscle. A thorough understanding of this biology could reveal previously undocumented DTC vulnerabilities that can be exploited to prevent metastasis in other more susceptible tissues.

骨骼肌长期以来一直被认为是播散性肿瘤细胞（DTC）的不适宜生存的场所。然而，它的抗转移性质却未能得到彻底的机制检验。在这里，我们发现 DTC 在小鼠和人类的骨骼肌中运输并持续存在，这提出了该组织如何抑制定植的问题。小鼠和器官培养模型的结果以及代谢组学分析表明，骨骼肌对 DTC 施加持续的氧化应激，从而损害其增殖。功能研究表明，通过活性氧的化学遗传学诱导破坏氧化还原稳态，可以减缓更肥沃的器官（肺）的增殖。相反，通过肿瘤或宿主线粒体中过氧化氢酶的异位表达增强肿瘤细胞的抗氧化潜力，从而实现骨骼肌的稳健定植。这些发现揭示了 DTC 所面临的严重代谢瓶颈，并由骨骼肌维持。彻底了解这种生物学特性可以揭示以前未记录的 DTC 漏洞，这些漏洞可用于防止其他更易受影响的组织中的转移。