ATP酶铜转运蛋白α介导的铜死亡途径及在肿瘤治疗中的价值

doi:10.6040/j.issn.1671-7554.0.2025.1013

摘要/Abstract

摘要： ATP酶铜转运蛋白α(ATPase copper transporting alpha, ATP7A)是维持细胞内铜离子稳态的核心地位转运蛋白,其在肿瘤中的异常表达与化疗耐药密切相关。铜死亡作为一种新发现的铜依赖性细胞死亡方式,为克服肿瘤耐药提供了新思路。然而,ATP7A如何介导铜死亡及其在肿瘤治疗中的转化价值尚缺乏系统性总结。本文聚焦ATP7A在铜死亡中的双重角色,围绕ATP7A介导的铜死亡通路,从生理功能与ATP7A在铜稳态中的作用、ATP7A在肿瘤化疗耐药中的机制、ATP7A调控铜死亡的核心分子通路以及靶向 ATP7A-铜死亡轴的抗肿瘤策略与应用前景,整合近年高水平研究,系统阐述其作为肿瘤治疗靶点的潜在价值与挑战,旨在为今后开发基于ATP7A-铜死亡轴的精准抗肿瘤策略提供理论依据与研究方向。

关键词: ATP酶铜转运蛋白α, 铜死亡, 铜稳态, 肿瘤治疗, 耐药性

Abstract: The ATPase copper transporting alpha(ATP7A)protein plays a pivotal role in maintaining intracellular copper ion homeostasis, and its aberrant expression in tumors is closely associated with chemoresistance. Cuproptosis, a newly discovered copper-dependent form of cell death, offers innovative strategies for overcoming tumor resistance. However, a systematic overview of how ATP7A mediates cuproptosis and its translational value in cancer therapy is lacking. This review focuses on the dual role of ATP7A in cuproptosis, encompassing the ATP7A-mediated cuproptotic pathway, its physiological functions, and role in copper homeostasis, the mechanisms of ATP7A in tumor chemoresistance, the core molecular pathways regulated by ATP7A in cuproptosis, and the therapeutic strategies targeting the ATP7A-cuproptosis axis in cancer. Integrating high-quality research from recent years, this paper systematically elucidates the potential value and challenges of ATP7A as a therapeutic target in cancer, aiming to provide a theoretical basis and direction for future research in developing precision anti-tumor strategies based on the ATP7A-cuproptosis axis.

Key words: ATP7A, Cuproptosis, Copper homeostasis, Cancer therapy, Drug resistance

中图分类号:

R730.5

林明霞,刘桂斌,马燕花,连曌昱,任洋洋. ATP酶铜转运蛋白α介导的铜死亡途径及在肿瘤治疗中的价值[J]. 山东大学学报 (医学版), 2026, 64(4): 117-124.

LIN Mingxia, LIU Guibin, MA Yanhua, LIAN Zhaoyu, REN Yangyang. ATPase copper transporting alpha mediated cuproptosis pathway and its value in cancer therapy[J]. Journal of Shandong University (Health Sciences), 2026, 64(4): 117-124.

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