武汉大学闫伟团队取得一项新突破。他们揭示了花生四烯酸触发原发肿瘤分泌亚精胺合成酶，诱导辐照后骨骼肌无力。这一研究成果于2025年6月19日发表在国际顶尖学术期刊《细胞—代谢》上。

该课题组发现癌细胞通过小的细胞外囊泡分泌更多的亚精胺合成酶（SRM）酶，从而引发放疗后骨骼肌无力。从机制上说，辐射触发的花生四烯酸（ArA）积累会提高SRM蛋白的ISG酰化，促进SRM从原发肿瘤包装到细胞外囊泡。循环SRM以依赖eIF5A的方式导致骨骼肌亚精胺积累和I型胶原纤维的生物合成。

然而，氯沙坦治疗阻断了SRM的ISG酰化及其随后的分泌。总的来说，他们的发现确定了ArA在放疗时循环SRM分泌的协同作用，通过重新连接多胺代谢加重骨骼肌纤维化，揭示了放射治疗介导的骨骼肌无力与氯沙坦联合治疗时的缓解。

研究人员表示，放疗降低了癌症复发和死亡的风险，但同时伴有细胞纤维化、虚弱等多重副作用，严重影响了患者的生活质量。然而，其基本机制定义不清。

附：英文原文

Title: Arachidonic acid triggers spermidine synthase secretion from primary tumor to induce skeletal muscle weakness upon irradiation

Author: Xiaohui Zhang, Zhongliang Nie, Shuang Wang, Yuxi Ma, Dan Han, Ting Hu, Liu Liu, Liying Men, Tao Zhang, Xiaoting Wu, Xu Li, Sheng Hu, Meng Yuan, Liu Liu, Chaoqun Wang, Ping Xu, Limin Xiang, Jiao Liu, Yong Zhang, Dahai Zhu, Hehua Lei, Limin Zhang, Xiangpan Li, Yanxia Zhao, Wei Yan

Issue&Volume: 2025-06-19

Abstract: Radiotherapy reduces the risk of cancer recurrence and death, but the fact that it's accompanied by multiple side effects including muscle fibrosis and weakness, seriously affects the life quality of patients. However, the underlying mechanism is poorly defined. Here, we identify that cancer cells secrete more spermidine synthase (SRM) enzyme through small extracellular vesicles to trigger skeletal muscle weakness upon radiotherapy. Mechanistically, irradiation-triggered arachidonic acid (ArA) accumulation elevates the ISGylation of the SRM protein, facilitating SRM packaging into extracellular vesicles from the primary tumor. Circulating SRM results in spermidine accumulation in skeletal muscle and type I collagen fiber biosynthesis in an eIF5A-dependent manner. However, losartan treatment blocks the ISGylation of SRM and its subsequent secretion. Collectively, our findings determine that ArA functions in concert for circulating SRM secretion upon radiotherapy, which aggravates skeletal muscle fibrosis through rewiring polyamine metabolism, shedding light on the alleviation of radiotherapy-mediated muscle weakness when combined with losartan treatment.

DOI: 10.1016/j.cmet.2025.05.013

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00269-4