Vitcylation of Lysine: The Novel Mechanism of Vitamin C in Tumor Treatment

Vitamin C (vitC), an essential nutrient for human health, has critical roles in numerous biological processes. VitC’s potential in disease prevention and treatment is a focus of ongoing research. Recent clinical studies have highlighted its promising effects in combating various tumor diseases, thus spurring further exploration of its anti-tumor mechanisms. Historically, the known anti-tumor mechanisms of vitC have included redox regulation and epigenetic modifications. He et al. have now uncovered a novel pathway in which covalent modification directly targets immune signaling proteins ( Cell , 2025 , 188 , 1858–1877. DOI: 10.1016/j.cell.2025.01.043 ). These findings, particularly lysine vitcylation, substantially change the understanding of vitC’s mechanistic landscape. This Commentary comprehensively analyzes He’s study elucidating the key mechanisms underlying vitC’s anti-tumor efficacy. Furthermore, it thoroughly examines the newly proposed mechanism and discusses potential implications for clinical applications as well as future challenges.