Copper metabolism and cuproptosis in human malignancies: Unraveling the complex interplay for therapeutic insights.

Autor:	Abdullah KM; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA., Kaushal JB; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA., Takkar S; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA., Sharma G; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA., Alsafwani ZW; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA., Pothuraju R; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.; Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, 695014, Kerala, India., Batra SK; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA.; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA., Siddiqui JA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 Mar 07; Vol. 10 (5), pp. e27496. Date of Electronic Publication: 2024 Mar 07 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e27496
Abstrakt:	Copper, a vital trace element, orchestrates diverse cellular processes ranging from energy production to antioxidant defense and angiogenesis. Copper metabolism and cuproptosis are closely linked in the context of human diseases, with a particular focus on cancer. Cuproptosis refers to a specific type of copper-mediated cell death or copper toxicity triggered by disruptions in copper metabolism within the cells. This phenomenon encompasses a spectrum of mechanisms, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and perturbations in metal ion equilibrium. Mechanistically, cuproptosis is driven by copper binding to the lipoylated enzymes within the tricarboxylic acid (TCA) cycle. This interaction participates in protein aggregation and proteotoxic stress, ultimately culminating in cell death. Targeting copper metabolism and its associated pathways in cancer cells hold therapeutic potential by selectively targeting and eliminating cancerous cells. Strategies to modulate copper levels, enhance copper excretion, or interfere with cuproptotic pathways are being explored to identify novel therapeutic targets for cancer therapy and improve patient outcomes. Understanding the relationship between cuproptosis and copper metabolism in human malignancies remains an active area of research. This review provides a comprehensive overview of the association among copper metabolism, copper homeostasis, and carcinogenesis, explicitly emphasizing the cuproptosis mechanism and its implications for cancer pathogenesis. Additionally, we emphasize the therapeutic aspects of targeting copper and cuproptosis for cancer treatment. Competing Interests: SKB is co-founder of Sanguine Diagnostics and Therapeutics, Inc. Other authors declare no competing interest. (© 2024 The Authors.)
Databáze:	MEDLINE
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