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作者

Xinjing Liu, Jian Liu, Wenqing Chen, Jimei Zhang, Yiju Wei, Lili Sun

作者单位

Affiliations ¹ Shandong Cancer Hospital, School of Life Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China. ² School of Laboratory Animal and Shandong Laboratory Animal Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China. ³ Cancer Biology Institute, Baotou Medical College, Baotou, 014040, Inner Mongolia Autonomous Region, China. ⁴ School of Pharmacy,Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China. ⁵ Shandong Provincial Qianfoshan Hospital, School of Life Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China. Electronic address: weiyiju@sdfmu.edu.cn. ⁶ Shandong Cancer Hospital, School of Life Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China. Electronic address: sunll@sdfmu.edu.cn.

刊名

Critical reviews in oncology/hematology

年份

2026

页码

105172

ISSN

1879-0461

关键词

Ferroptosis tumor ubiquitin-like modifications ubiquitination.

摘要

Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation, characterized by the inhibition of glutathione peroxidase 4 , glutathione depletion, and peroxidation of polyunsaturated fatty acids . Due to metabolic reprogramming and impaired antioxidant defenses, tumor cells exhibit heightened sensitivity to ferroptosis, positioning it as a promising therapeutic target for cancer. Within the cellular protein regulatory network, post-translational modifications -par...更多

Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation, characterized by the inhibition of glutathione peroxidase 4 , glutathione depletion, and peroxidation of polyunsaturated fatty acids . Due to metabolic reprogramming and impaired antioxidant defenses, tumor cells exhibit heightened sensitivity to ferroptosis, positioning it as a promising therapeutic target for cancer. Within the cellular protein regulatory network, post-translational modifications -particularly ubiquitination and ubiquitin-like modifications -serve as molecular switches by modulating the stability of key proteins such as GPX4 and SLC7A11. This review systematically dissects how E3 ubiquitin ligases and deubiquitinating enzymes orchestrate redox homeostasis and iron metabolism, through site-specific ubiquitination of critical proteins. Furthermore, we highlight the development of small-molecule inhibitors targeting these modifications, emphasizing their potential to disrupt ferroptosis resistance pathways. By integrating mechanistic insights with therapeutic applications, this study not only elucidates the dynamic complexity of ubiquitin-mediated regulatory networks but also proposes innovative strategies leveraging Ub/Ubl modifications for targeted cancer therapy. These findings provide a foundational theoretical framework and actionable research directions for advancing precision medicine in oncology.收起

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期刊