Abstract
Iron is an essential trace element for the human body, and its deficiency or excess can induce a variety of biological processes. Plenty of evidences have shown that iron metabolism is closely related to the occurrence and development of tumors. In addition, iron plays an important role in cell death, which is very important for the development of potential strategies for tumor treatment. Here, we reviewed the latest research about iron metabolism disorders in various types of tumors, the functions and properties of iron in ferroptosis and ferritinophagy, and new opportunities for iron-based on treatment methods for tumors, providing more information regarding the prevention and treatment of tumors.
Highlights
Iron (Fe) is one of the most abundant elements in the earth’s crust [1]
Other studies have shown that targeting transferrin receptor (TFR1) can suppress tumor progression, such as MiR-107 can inhibit the proliferation, migration, and invasion of SW620 cells by targeting TFR1 [34]; MiR-148a could reduce the proliferation of liver cancer cells by targeting TFR1 [32]; EGFR regulates cellular iron homeostasis by regulating the redistribution of TFR1, and promotes the development of non-small cell lung cancer [60]
IRP1 and IRP2 are strictly regulated in tumors, and preferably modulate tumor progression in an iron-engaged signaling pathways, such as IRP2 is regulated by ubiquitin ligase FBXL5, which mediated IRP2 ubiquitination and degradation under the condition of sufficient iron; Dysregulation of FBXL5 has been associated with a poor prognosis of human hepatocellular carcinoma [78]; A recent study demonstrated that FBXL5 is stabilized and increases iron levels when iron is at low levels, facilitating the production of [2Fe2S] cluster, which can serve as an FBXL5 cofactor, and by incorporating into the Cterminal LRR domain of FBXL5, and only when oxygen level is high enough to maintain the [2Fe2S] cluster in its oxidized [2Fe2S]2+ state could the SCFFBXL5 E3 ligase recruits IRP2 as a substrate for polyubiquination and degradation
Summary
Qianqian Guo 1†, Liwen Li 3†, Shanshan Hou 4, Ziqiao Yuan 5, Chenhui Li 3, Wenzhou Zhang 1*, Lufeng Zheng 3* and Xiaoman Li 2*. Reviewed by: Richard Possemato, NYU Grossman School of Medicine, United States Keith R. Iron is an essential trace element for the human body, and its deficiency or excess can induce a variety of biological processes. Plenty of evidences have shown that iron metabolism is closely related to the occurrence and development of tumors. Iron plays an important role in cell death, which is very important for the development of potential strategies for tumor treatment. We reviewed the latest research about iron metabolism disorders in various types of tumors, the functions and properties of iron in ferroptosis and ferritinophagy, and new opportunities for iron-based on treatment methods for tumors, providing more information regarding the prevention and treatment of tumors
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