Western Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea.
Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea; Department of Biomedical Science, General Graduate School, CHA University, Pocheon, Republic of Korea.
Cancer Lett. 2024 Mar 31;585:216645. doi: 10.1016/j.canlet.2024.216645. Epub 2024 Jan 26.
The TP53 gene, encoding the p53 protein, has been a focal point of research since its 1979 discovery, playing a crucial role in tumor suppression. Ferroptosis, a distinct form of cell death characterized by lipid peroxide accumulation, has gained prominence since its recognition in 2012. Recent studies have unveiled an intriguing connection between p53 and ferroptosis, with implications for cancer therapy. Recent research underscores p53 as a novel target for cancer therapy, influencing key metabolic processes in ferroptosis. Notably, p53 represses the expression of the cystine-glutamate antiporter SLC7A11, supporting p53-mediated tumor growth suppression. Furthermore, under metabolic stress, p53 mitigates ferroptosis sensitivity, aiding cancer cells in coping and delaying cell death. This dynamic interplay between p53 and ferroptosis has far-reaching implications for various diseases, particularly cancer. This review provides a comprehensive overview of ferroptosis in cancer cells, elucidating p53's role in regulating ferroptosis, and explores the potential of targeting p53 to induce ferroptosis for cancer therapy. Understanding this complex relationship between p53 and ferroptosis offers a promising avenue for developing innovative cancer treatments.
TP53 基因，编码 p53 蛋白，自 1979 年发现以来一直是研究的焦点，在肿瘤抑制中起着关键作用。铁死亡是一种独特的细胞死亡形式，其特征是脂质过氧化物的积累，自 2012 年被认识以来，其重要性日益凸显。最近的研究揭示了 p53 与铁死亡之间的有趣联系，这对癌症治疗具有重要意义。最近的研究强调了 p53 作为癌症治疗的新靶点，影响铁死亡中的关键代谢过程。值得注意的是，p53 抑制胱氨酸-谷氨酸反向转运体 SLC7A11 的表达，支持 p53 介导的肿瘤生长抑制。此外，在代谢应激下，p53 减轻铁死亡敏感性，帮助癌细胞应对并延迟细胞死亡。p53 与铁死亡之间的这种动态相互作用对各种疾病，特别是癌症，具有深远的影响。本综述全面概述了癌细胞中的铁死亡，阐明了 p53 在调节铁死亡中的作用，并探讨了靶向 p53 诱导铁死亡用于癌症治疗的潜力。理解 p53 和铁死亡之间的这种复杂关系为开发创新的癌症治疗方法提供了一个有前途的途径。
