Liu Xiaoyu, Zhang Xinyu, Fan Yumei, Tan Ke
Ministry of Education Key Laboratory of Molecular and Cellular Biology, Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology, Hebei Research Center of the Basic Discipline of Cell Biology, Hebei Collaborative Innovation Center for Eco-Environment, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei, P.R. China.
Ministry of Education Key Laboratory of Molecular and Cellular Biology, Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology, Hebei Research Center of the Basic Discipline of Cell Biology, Hebei Collaborative Innovation Center for Eco-Environment, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei, P.R. China.
Vitam Horm. 2025;129:317-360. doi: 10.1016/bs.vh.2024.10.003. Epub 2024 Oct 24.
Iron is an essential trace element that plays a crucial role in various biological processes, including oxygen transport, DNA synthesis and cell proliferation. Iron homeostasis is a critical biological equilibrium that involves the balance of iron absorption, utilization, storage and excretion. Iron is intricately linked to the pathophysiology of cancer. Its dual role as a vital nutrient and a potential carcinogen highlights the complexity of iron's influence on tumorigenesis. Iron balance is finely tuned through a complex interplay of molecular components and regulatory mechanisms. Hepcidin, a liver-derived peptide hormone, is the principal regulator of systemic iron availability. Hepcidin exerts its effects by binding to the iron export protein ferroportin (FPN1), leading to its internalization and degradation, which in turn reduces the release of iron from macrophages and the intestinal absorption of dietary iron. In human cancers, the expression of hepcidin is significantly altered, leading to increased iron absorption and retention. Hepcidin has emerged as a significant player in cancer biology due to its potential as both a tumor suppressor and a promoter. Understanding the context-dependent role of hepcidin in cancer opens avenues for novel therapeutic strategies. Modulating hepcidin levels or its activity could be a potential approach to treat cancer, either by starving tumors of iron or by normalizing the iron-rich microenvironment to enhance the efficacy of existing cancer treatments. In this review, we provide a comprehensive overview of the critical functions of hepcidin in iron metabolism, summarize the upstream regulatory factors that control the expression of hepcidin, and delve deeply into the downstream signaling pathways and molecular mechanisms by which hepcidin regulates the tumorigenesis, as well as elucidate the promising potential of hepcidin as a novel therapeutic target in the treatment of cancer, underscoring the significance of understanding and harnessing the complex interplay between hepcidin, iron metabolism and cancer biology.
铁是一种必需的微量元素，在多种生物过程中发挥着关键作用，包括氧气运输、DNA合成和细胞增殖。铁稳态是一种关键的生物平衡，涉及铁的吸收、利用、储存和排泄的平衡。铁与癌症的病理生理学密切相关。它作为一种重要营养素和潜在致癌物的双重作用凸显了铁对肿瘤发生影响的复杂性。铁平衡通过分子成分和调节机制的复杂相互作用进行精细调节。铁调素是一种肝脏衍生的肽激素，是全身铁可用性的主要调节因子。铁调素通过与铁输出蛋白铁转运蛋白1（FPN1）结合发挥作用，导致其内化和降解，进而减少巨噬细胞中铁的释放和膳食铁的肠道吸收。在人类癌症中，铁调素的表达显著改变，导致铁吸收和潴留增加。由于铁调素兼具肿瘤抑制和促进作用的潜力，它已成为癌症生物学中的一个重要角色。了解铁调素在癌症中依赖于背景的作用为新的治疗策略开辟了道路。调节铁调素水平或其活性可能是治疗癌症的一种潜在方法，要么通过使肿瘤缺铁，要么通过使富含铁的微环境正常化来提高现有癌症治疗的疗效。在本综述中，我们全面概述了铁调素在铁代谢中的关键功能，总结了控制铁调素表达的上游调节因子，并深入探讨了铁调素调节肿瘤发生的下游信号通路和分子机制，以及阐明铁调素作为癌症治疗新靶点的潜在前景，强调了理解和利用铁调素、铁代谢与癌症生物学之间复杂相互作用的重要性。
