The Multifaceted Roles of Copper in Cancer: A Trace Metal Element with Dysregulated Metabolism, but Also a Target or a Bullet for Therapy.
The Multifaceted Roles of Copper in Cancer: A Trace Metal Element with Dysregulated Metabolism, but Also a Target or a Bullet for Therapy.
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铜在癌症中的多方面作用：一种代谢失调的微量金属元素，但也是治疗的靶点或子弹。
DOI：
10.3390/cancers12123594
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发表时间：
2020-12-01
期刊：
影响因子：
5.2
通讯作者：
Busser B
中科院分区：
文献类型：
--
作者：
Lelièvre P;Sancey L;Coll JL;Deniaud A;Busser B
铜是人类生命的必需元素。然而，它的氧化还原活性可能对细胞有害，这些细胞发展了高度协调的途径来螯合和运输铜通过细胞或生物体。由于铜在细胞生长和代谢所必需的功能中的重要作用，铜浓度经常在肿瘤中失调。在这篇综述中，我们描述了正常和癌症改变铜稳态的机制。此外，在此知识的基础上，我们不仅揭示了肿瘤学的铜相关诊断和预后标志物，还揭示了作用于铜稳态以对抗癌症的治疗策略。在人体内，铜（Cu）是大量细胞机制和信号通路中的主要和必不可少的参与者。铜参与氧化还原反应需要密切调节铜代谢，以避免毒性作用。在许多类型的癌症中，铜蛋白水平的变化已被证明。这些变化导致肿瘤内铜浓度的增加和铜的全身分布的改变。铜稳态的这种改变可能促进肿瘤生长或侵袭性，甚至可能赋予对治疗的抗性。一旦确定特征，铜代谢失调就可以精确定位几种有前途的生物标志物，可用于临床，具有预后或预测能力。癌细胞中改变的Cu代谢和肿瘤细胞对Cu的不同反应强烈支持开发破坏、消耗或增加肿瘤中Cu水平的治疗。Cu作为化学元素的金属性质是通过合成具有抗癌特性的纳米颗粒或铜基复合物来开发抗癌剂的关键。最后，这些新的治疗策略中的一些，如螯合剂或离子载体，已经在临床前环境中显示出有希望的结果，其他的已经在临床中。
Copper is an essential element for human life. However, its redox activity can be detrimental for the cell that developed highly coordinated pathways to chelate and traffic copper through the cell or the organism. Owing to its important role in functions essential for cell growth and metabolism, copper concentrations are frequently dysregulated in tumors. In this review, we describe normal and cancer-altered copper homeostasis mechanisms. Moreover, on the basis of this knowledge, we expose not only copper-related diagnostic and prognostic markers for oncology but also therapeutic strategies to act on copper homeostasis to fight against cancer. In the human body, copper (Cu) is a major and essential player in a large number of cellular mechanisms and signaling pathways. The involvement of Cu in oxidation–reduction reactions requires close regulation of copper metabolism in order to avoid toxic effects. In many types of cancer, variations in copper protein levels have been demonstrated. These variations result in increased concentrations of intratumoral Cu and alterations in the systemic distribution of copper. Such alterations in Cu homeostasis may promote tumor growth or invasiveness or may even confer resistance to treatments. Once characterized, the dysregulated Cu metabolism is pinpointing several promising biomarkers for clinical use with prognostic or predictive capabilities. The altered Cu metabolism in cancer cells and the different responses of tumor cells to Cu are strongly supporting the development of treatments to disrupt, deplete, or increase Cu levels in tumors. The metallic nature of Cu as a chemical element is key for the development of anticancer agents via the synthesis of nanoparticles or copper-based complexes with antineoplastic properties for therapy. Finally, some of these new therapeutic strategies such as chelators or ionophores have shown promising results in a preclinical setting, and others are already in the clinic.
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影响因子：
2
作者：
Battistelli, S.;Stefanoni, M.;Vittoria, A.
通讯作者：
Vittoria, A.
DOI：
10.1073/pnas.1910722117
发表时间：
2020-01-28
影响因子：
11.1
作者：
Blockhuys, Stephanie;Zhang, Xiaolu;Wittung-Stafshede, Pernilla
通讯作者：
Wittung-Stafshede, Pernilla
影响因子：
6.4
作者：
Albinger-Hegyi, Andrea;Stoeckli, Sandro J.;Hegyi, Ivan
通讯作者：
Hegyi, Ivan
DOI：
10.1016/j.bbrc.2016.12.148
发表时间：
2017-01-29
影响因子：
3.1
作者：
Blockhuys, Stephanie;Wittung-Stafshede, Pernilla
通讯作者：
Wittung-Stafshede, Pernilla
影响因子：
15
作者：
Boal AK;Rosenzweig AC
通讯作者：
Rosenzweig AC