Research progress of ferroptosis and its role in liver cancer_West China Medical Journal

Authors：

LIU Bowen ¹ , LI Xiaobin ¹ , MA Guiping ¹ , YI Fan ² , LI Feng ¹ , SUN Tong ¹ , PANG Xu ¹ ,  HU Shiping ¹

1. Department of Hepatology, Shenzhen Hospital of Beijing University of Chinese Medicine (Longgang), Shenzhen, Guangdong 518172, P. R. China;
2. Department of Dermatology, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing 100010, P. R. China;

Corresponding author：

HU Shiping, Email: szhushiping@21cn.com

Keywords：

Ferroptosis; liver cancer; mechanism; lipid peroxidation; iron metabolism; research progress

DOI：

10.7507/1002-0179.202404201

Video：

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Abstract Full text Figures/Tables Video References Cited by

Ferroptosis, as a new form of programmed cell death, affects the occurrence, progression and treatment of liver cancer. In this paper, the discovery, characteristics, regulatory mechanisms, inhibitors, inducers, and detection indicators of ferroptosis were systematically summarized and analyzed, and the effects of ferroptosis on the progression, metastasis, treatment, and prognosis of liver cancer were summarized. Finally, it was concluded that targeting ferroptosis is a promising treatment strategy for liver cancer.

Citation： LIU Bowen, LI Xiaobin, MA Guiping, YI Fan, LI Feng, SUN Tong, PANG Xu, HU Shiping. Research progress of ferroptosis and its role in liver cancer. West China Medical Journal, 2024, 39(7): 1156-1161. doi: 10.7507/1002-0179.202404201 Copy

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9. Xu S, He Y, Lin L, et al. The emerging role of ferroptosis in intestinal disease. Cell Death Dis, 2021, 12(4): 289.
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19. Dixon SJ, Stockwell BR. The role of iron and reactive oxygen species in cell death. Nat Chem Biol, 2014, 10(1): 9-17.
20. Wang H, Cheng Y, Mao C, et al. Emerging mechanisms and targeted therapy of ferroptosis in cancer. Mol Ther, 2021, 29(7): 2185-2208.
21. Doll S, Proneth B, Tyurina YY, et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol, 2017, 13(1): 91-98.
22. Skoupilová H, Michalová E, Hrstka R. Ferroptosis as a new type of cell death and its role in cancer treatment. Klin Onkol, 2018, 31(Suppl 2): 21-26.
23. Luo Y, Bai XY, Zhang L, et al. Ferroptosis in cancer therapy: mechanisms, small molecule inducers, and novel approaches. Drug Des Devel Ther, 2024, 18: 2485-2529.
24. Jiang S, Zhang G, Ma Y, et al. Ferroptosis in hepatocellular carcinoma, from mechanism to effect. Front Oncol, 2024, 14: 1350011.
25. Du L, Wu Y, Jia Q, et al. Autophagy suppresses ferroptosis by degrading TFR1 to alleviate cognitive dysfunction in mice with SAE. Cell Mol Neurobiol, 2023, 43(7): 3605-3622.
26. Qu L, He X, Tang Q, et al. Iron metabolism, ferroptosis, and lncRNA in cancer: knowns and unknowns. J Zhejiang Univ Sci B, 2022, 23(10): 844-862.
27. Shen H, Zhai L, Wang G. Hepcidin regulates neuronal ferroptosis: a mechanism for postoperative cognitive dysfunction. J Biochem Mol Toxicol, 2022, 36(11): e23190.
28. Feng H, Stockwell BR. Unsolved mysteries: how does lipid peroxidation cause ferroptosis?. PLoS Biol, 2018, 16(5): e2006203.
29. Liu M, Kong XY, Yao Y, et al. The critical role and molecular mechanisms of ferroptosis in antioxidant systems: a narrative review. Ann Transl Med, 2022, 10(6): 368.
30. Hong Y, Feng J, Dou Z, et al. Berberine as a novel ACSL4 inhibitor to suppress endothelial ferroptosis and atherosclerosis. Biomed Pharmacother, 2024, 177: 117081.
31. Hao J, Wang T, Cao C, et al. LPCAT3 exacerbates early brain injury and ferroptosis after subarachnoid hemorrhage in rats. Brain Res, 2024, 1832: 148864.
32. Yu H, Guo P, Xie X, et al. Ferroptosis, a new form of cell death, and its relationships with tumourous diseases. J Cell Mol Med, 2017, 21(4): 648-657.
33. Fearnhead HO, Vandenabeele P, Vanden Berghe T. How do we fit ferroptosis in the family of regulated cell death?. Cell Death Differ, 2017, 24(12): 1991-1998.
34. Liu J, Kang R, Tang D. Signaling pathways and defense mechanisms of ferroptosis. FEBS J, 2022, 289(22): 7038-7050.
35. Seibt TM, Proneth B, Conrad M. Role of GPX4 in ferroptosis and its pharmacological implication. Free Radic Biol Med, 2019, 133: 144-152.
36. Hu Q, Zhang Y, Lou H, et al. GPX4 and vitamin E cooperatively protect hematopoietic stem and progenitor cells from lipid peroxidation and ferroptosis. Cell Death Dis, 2021, 12(7): 706.
37. Yao Y, Chen Z, Zhang H, et al. Selenium-GPX4 axis protects follicular helper T cells from ferroptosis. Nat Immunol, 2021, 22(9): 1127-1139.
38. Yang WS, SriRamaratnam R, Welsch ME, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell, 2014, 156(1/2): 317-331.
39. 黄煜超, 叶芬. 铁死亡在肿瘤发展和治疗中的作用机制. 肿瘤学杂志, 2023, 29(2): 150-155.
40. Jiang L, Kon N, Li T, et al. Ferroptosis as a p53-mediated activity during tumour suppression. Nature, 2015, 520(7545): 57-62.
41. Zhang F, Xiao Y, Huang Z, et al. Upregulation of GPX4 drives ferroptosis resistance in scleroderma skin fibroblasts. Free Radic Biol Med, 2024, 221: 23-30.
42. 王欣雨, 岳源, 胡译戈, 等. 肿瘤治疗中铁死亡的作用. 中华肿瘤防治杂志, 2023, 30(13): 820-826.
43. Liang C, Zhang X, Yang M, et al. Recent progress in ferroptosis inducers for cancer therapy. Adv Mater, 2019, 31(51): e1904197.
44. Liu M, Fan Y, Li D, et al. Ferroptosis inducer erastin sensitizes NSCLC cells to celastrol through activation of the ROS-mitochondrial fission-mitophagy axis. Mol Oncol, 2021, 15(8): 2084-2105.
45. Su Y, Zhao B, Zhou L, et al. Ferroptosis, a novel pharmacological mechanism of anti-cancer drugs. Cancer Lett, 2020, 483: 127-136.
46. Zhang Y, Tan H, Daniels JD, et al. Imidazole ketone erastin induces ferroptosis and slows tumor growth in a mouse lymphoma model. Cell Chem Biol, 2019, 26(5): 623-633. e9.
47. Song X, Zhu S, Chen P, et al. AMPK-mediated BECN1 phosphorylation promotes ferroptosis by directly blocking system Xc- activity. Curr Biol, 2018, 28(15): 2388-2399.
48. Yang WS, Stockwell BR. Ferroptosis: death by lipid peroxidation. Trends Cell Biol, 2016, 26(3): 165-176.
49. Sun Y, Berleth N, Wu W, et al. Fin56-induced ferroptosis is supported by autophagy-mediated GPX4 degradation and functions synergistically with mTOR inhibition to kill bladder cancer cells. Cell Death Dis, 2021, 12(11): 1028.
50. 张申武, 单新竹, 孙新新, 等. 基于纳米递送技术诱导肿瘤铁死亡的研究进展. 药学学报, 2022, 57(1): 36-45, 275.
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