Department of Plastic Surgery, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, 430060, Hubei Province, China.
Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Int J Biol Sci. 2024 Sep 9;20(12):4872-4887. doi: 10.7150/ijbs.98806. eCollection 2024.
Breast cancer (BC) persists as a highly prevalent malignancy in females, characterized by diverse molecular signatures and necessitating personalized therapeutic approaches. The equilibrium of copper within the organism is meticulously maintained through regulated absorption, distribution, and elimination, underpinning not only cellular equilibrium but also various essential biological functions. The process of cuproptosis is initiated by copper's interaction with lipoylases within the tricarboxylic acid (TCA) cycle, which triggers the conglomeration of lipoylated proteins and diminishes the integrity of Fe-S clusters, culminating in cell demise through proteotoxic stress. In BC, aberrations in cuproptosis are prominent and represent a crucial molecular incident that contributes to the disease progression. It influences BC cell metabolism and affects critical traits such as proliferation, invasiveness, and resistance to chemotherapy. Therapeutic strategies that target cuproptosis have shown promising antitumor efficacy. Moreover, a plethora of cuproptosis-centric genes, including cuproptosis-related genes (CRGs), CRG-associated non-coding RNAs (ncRNAs), and cuproptosis-associated regulators, have been identified, offering potential for the development of risk assessment models or diagnostic signatures. In this review, we provide a comprehensive exposition of the fundamental principles of cuproptosis, its influence on the malignant phenotypes of BC, the prognostic implications of cuproptosis-based markers, and the substantial prospects of exploiting cuproptosis for BC therapy, thereby laying a theoretical foundation for targeted interventions in this domain.
乳腺癌（BC）仍然是女性中高发的恶性肿瘤，其特征是具有不同的分子特征，需要个性化的治疗方法。生物体中的铜平衡是通过调节吸收、分布和消除来精细维持的，不仅支撑着细胞平衡，还支撑着各种重要的生物学功能。铜死亡的过程是由铜与三羧酸 (TCA) 循环中的脂酰酶相互作用引发的，这触发了脂酰化蛋白的聚集，并降低了 Fe-S 簇的完整性，最终通过蛋白毒性应激导致细胞死亡。在 BC 中，铜死亡的异常是显著的，是导致疾病进展的关键分子事件。它影响 BC 细胞代谢，并影响增殖、侵袭性和对化疗的耐药性等关键特征。针对铜死亡的治疗策略显示出有希望的抗肿瘤疗效。此外，已经确定了大量以铜死亡为中心的基因，包括铜死亡相关基因 (CRGs)、CRG 相关非编码 RNA (ncRNAs) 和铜死亡相关调节剂，为开发风险评估模型或诊断标志物提供了潜力。在这篇综述中，我们全面阐述了铜死亡的基本原理、它对 BC 恶性表型的影响、基于铜死亡的标志物的预后意义，以及利用铜死亡治疗 BC 的巨大前景，为这一领域的靶向干预奠定了理论基础。
