Iron metabolism: State of the art in hypoxic cancer cell biology.

Abstract

The tumor microenvironment (TME) promotes the malignant transformation of cancer cells, mainly through metabolic reprogramming. As one of the most prominent features of the TME, hypoxia contributes to cancer cell death resistance, invasion, metastasis, and therapy-resistant phenotypes. As an important cofactor for various enzymes, iron is essential for ATP generation, antioxidant protein function, and DNA-damage repair in hypoxic cancer cells. Iron metabolism, as a promoter of aggressive hypoxic cancer cell biology, has attracted an increasing amount of attention. Iron utilization, storage, and efflux are enhanced in hypoxic cancer cells, which further contributes to cancer cell proliferation, metastasis, ferroptosis resistance, and immune escape. This review describes the relationship between iron metabolism and proliferation, metastasis, and ferroptosis of hypoxic cancer cells, as well as several iron-targeted cancer therapy strategies. Understanding the hypoxia-specific regulatory mechanism of iron metabolism could aid the development of targeted therapy against refractory hypoxic cancer cells.

• Authors: Sai Liu, Xiongfeng Cao, Dongqing Wang, Haitao Zhu
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 723 Pg. 109199 (07 15 2022) ISSN: 1096-0384 [Electronic] United States
• PMID: 35398290 (Publication Type: Journal Article, Review, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Iron

Topics

• Ferroptosis
• Humans
• Hypoxia
• Iron (metabolism)
• Neoplasms (genetics)
• Tumor Microenvironment