Targeting iron regulatory protein 2 (IRP2) to disrupt iron metabolism enhances radiosensitivity through mitochondrial dysfunction in breast cancer cells.

IF 7 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-07-31 DOI:10.1038/s41420-025-02653-z

Ye Yeong Jeong, Jieon Hwang, Areum Park, Sungmin Cho, Inyoung Cho, Soseul Won, You Me Shin, Sung Eun Kim, Chan Hoon Maeng, Jaemoon Yang, Minhee Ku, Hyuk Lee, Sang Joon Shin

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Abstract

Iron regulatory protein (IRP2) plays a key role in regulating iron metabolism and enables cell survival by activating mitochondrial function. Targeting IRP2 to disrupt iron homeostasis is a promising strategy for enhancing the efficacy of cancer treatments. Depletion of IRP2 in breast cancer (BC) cells is associated with sensitivity to radiation therapy (RT), and inhibition of IRP2 prior to RT significantly reduces cell viability compared with radiation treatment alone. This combined therapeutic effects of IRP2 inhibition and radiation treatment were observed in parental and radioresistant cancer cells, significantly enhancing the proportion of cell death. In conclusion, this study proposes that the genetic or pharmacological inhibition of IRP2 in BC cells may serve as a novel therapeutic strategy for increasing radiosensitivity and overcoming resistance by inducing mitochondrial dysfunction.

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靶向铁调节蛋白2 （IRP2）破坏铁代谢，通过线粒体功能障碍增强乳腺癌细胞的放射敏感性。

铁调节蛋白（IRP2）在调节铁代谢中起关键作用，并通过激活线粒体功能使细胞存活。靶向IRP2破坏铁稳态是一种很有前景的提高癌症治疗效果的策略。乳腺癌（BC）细胞中IRP2的缺失与放射治疗（RT）的敏感性相关，与单独放射治疗相比，在放疗前抑制IRP2显著降低细胞活力。在亲代和放射耐药癌细胞中观察到IRP2抑制和放射治疗的联合治疗效果，显著提高细胞死亡比例。总之，本研究提出，基因或药物抑制BC细胞中的IRP2可能作为一种新的治疗策略，通过诱导线粒体功能障碍来增加放射敏感性和克服耐药性。

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 Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.