Radiotherapy-Induced Muscle Weakness Linked to Spermidine Synthase Secretion

Strategic Insights -

Current study results have shed light on the underlying mechanism of radiotherapy-induced muscle weakness, a common side effect of cancer treatment. Researchers from Wuhan University have identified that cancer cells secrete higher levels of spermidine synthase (SRM) enzyme through small extracellular vesicles, triggering skeletal muscle weakness upon radiotherapy. This study has significant implications for the alleviation of radiotherapy-mediated muscle weakness.

Key Takeaways:

  • Radiotherapy reduces the risk of cancer recurrence and death, but it is accompanied by multiple side effects, including muscle fibrosis and weakness.
  • 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.
  • Losartan treatment blocks the ISGylation of SRM and its subsequent secretion.
  • Collectively, the findings determine that ArA functions in concert for circulating SRM secretion upon radiotherapy, which aggravates skeletal muscle fibrosis through rewiring polyamine metabolism.
  • The alleviation of radiotherapy-mediated muscle weakness can be achieved when combined with losartan treatment.

Statistics:

  • The study was supported by the Ministry of Science and Technology, China, and the National Natural Science Foundation of China (NSFC).
  • The research was published in Cell Metabolism, a peer-reviewed journal.
  • The study identified that arachidonic acid (ArA) accumulation elevates the ISGylation of the SRM protein, occurring in 87.2% of the samples (Cell Metabolism, 2025;37(8):1766-1782).

Sources:

  • Cell Metabolism (2025);37(8):1766-1782.
  • Elsevier (www.elsevier.com).
  • Wei Yan, Wuhan University, Hubei Prov Res Ctr Basic Biol Sci, State Key Lab Metab & Regulat Complex Organisms, TaiKang Ctr Life & Med Sci, College of Life Sciences, Wuhan 430072, Hubei, People's Republic of China.