The solute carrier family 11 transporters: a bridge between iron homeostasis and tumor biology.

IF 8.2 2区生物学 Q1 CELL BIOLOGY

Cell Communication and Signaling Pub Date : 2025-07-10 DOI:10.1186/s12964-025-02293-x

Ruchira Banerjee, Bintee Bintee, Mukesh Kumar Manickasamy, Shristy Jha, Mohammed S Alqahtani, Mohamed Abbas, Arul Goel, Gautam Sethi, Zhaowu Ma, Ajaikumar B Kunnumakkara

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引用次数: 0

Abstract

Iron is an essential trace element in the human body, and its imbalance is closely linked to the initiation and progression of various malignancies. The solute carrier family 11 (SLC11) transporters, comprising SLC11A1 and SLC11A2, play pivotal roles in iron metabolism and cellular homeostasis, processes intricately linked to oncogenesis. SLC11A1, primarily expressed in macrophages, modulates immune responses and reshapes the tumor microenvironment, while SLC11A2, a ubiquitous iron transporter, regulates dietary iron absorption and ferroptosis, an iron-dependent form of programmed cell death. Dysregulation of these transporters is associated with tumor initiation, progression, metastasis, and therapy resistance. In this review, we provide an overview of the physiological functions of SLC11 transporters in iron metabolism and their pathological roles in cancer biology. Emerging evidence highlights their involvement in key oncogenic pathways, including p53, JAK/STAT, Wnt and HIF signaling. Pharmacological and genetic interventions targeting SLC11 transporters have shown the potential to disrupt tumor progression and enhance treatment efficacy. By exploring the intricate roles of SLC11A1 and SLC11A2 in cancer progression, this review offers insights into their potential as biomarkers and therapeutic targets, paving the way for innovative cancer treatment strategies.

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溶质载体家族11转运蛋白：铁稳态与肿瘤生物学之间的桥梁。

铁是人体必需的微量元素，其失衡与各种恶性肿瘤的发生和发展密切相关。溶质载体家族11 （SLC11）转运蛋白，包括SLC11A1和SLC11A2，在铁代谢和细胞稳态中起关键作用，这一过程与肿瘤的发生有着复杂的联系。SLC11A1主要在巨噬细胞中表达，调节免疫反应并重塑肿瘤微环境，而SLC11A2是一种普遍存在的铁转运蛋白，调节膳食铁吸收和铁凋亡，这是一种铁依赖性的程序性细胞死亡形式。这些转运蛋白的失调与肿瘤的发生、进展、转移和治疗抵抗有关。本文就SLC11转运体在铁代谢中的生理功能及其在肿瘤生物学中的病理作用作一综述。新出现的证据强调了它们参与关键的致癌途径，包括p53、JAK/STAT、Wnt和HIF信号通路。针对SLC11转运体的药物和遗传干预已显示出破坏肿瘤进展和提高治疗效果的潜力。通过探索SLC11A1和SLC11A2在癌症进展中的复杂作用，本综述提供了它们作为生物标志物和治疗靶点的潜力，为创新癌症治疗策略铺平了道路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Communication and Signaling CELL BIOLOGY-

CiteScore

11.00

自引率

0.00%

发文量

180

期刊介绍： Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.