Copper is an important trace element for maintaining key biological functions such as cellular respiration, nerve conduction, and antioxidant defense. Maintaining copper homeostasis is critical for human health, and its imbalance has been linked to various diseases, especially cancer. Cuproptosis, a novel mechanism of copper-induced cell death, provides new therapeutic opportunities for metal ion regulation to interact with cell fate. This review provides insights into the complex mechanisms of copper metabolism, the molecular basis of cuproptosis, and its association with cancer development. We assess the role of cuproptosis-related genes (CRGs) associated with tumorigenesis, their importance as prognostic indicators and therapeutic targets, and the impact of copper homeostasis on the tumor microenvironment (TME) and immune response. Ultimately, this review highlights the complex interplay between copper, cuproptosis, and cancer immunotherapy.
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http://dx.doi.org/10.1186/s40364-024-00677-8 | DOI Listing |
Free Radic Biol Med
January 2025
Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, China; Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230601, China. Electronic address:
The emergence of cuproptosis, a novel form of regulated cell death, is induced by an excess of copper ions and has been associated with the progression of multiple diseases, including liver injury, cardiovascular disease, and neurodegenerative disorders. However, there are currently no inhibitors available for targeting specific cuproptosis-related pathways in therapy. Here, the compound merestinib (MTB) has been identified as a strong inhibitor of cuproptosis through screening of a kinase inhibitor library.
View Article and Find Full Text PDFEcotoxicol Environ Saf
January 2025
State Key Laboratory of Swine and Poultry Breeding Industry, Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chendu 611130, PR China. Electronic address:
Copper is an essential trace element in biological systems, playing a key role in various physiological functions, including redox reactions and energy metabolism. However, an imbalance in copper homeostasis can induce oxidative stress, mitochondrial dysfunction, and inhibition of the ubiquitin-proteasome system, ultimately leading to significant cytotoxicity and cell death. According to recent research, copper can bind to lipoylation sites on proteins involved in the tricarboxylic acid cycle, causing aggregation of lipoylated proteins, the loss of Fe-S cluster proteins, proteotoxic stress, and ultimately, cell death.
View Article and Find Full Text PDFFood Chem
December 2024
Atomic and Mass Spectrometry - A&MS Research Unit, Department of Chemistry, Ghent University, 9000 Ghent, Belgium. Electronic address:
The disruption of Cu homeostasis is associated with the pathogenesis of many diseases and can result in alterations in Cu isotope fractionation. Changes in the Cu isotope ratio (Cu/Cu) of body fluids and tissues have been observed in liver disorders, cancers, and other diseases, displaying diagnostic/prognostic potential. However, it is not entirely clear whether certain physiological or lifestyle factors may also influence the bodily Cu isotopic composition, potentially obfuscating the signature of the pathology.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Chemistry, University of California, Berkeley, CA 94720.
Copper is an essential nutrient for sustaining vital cellular processes spanning respiration, metabolism, and proliferation. However, loss of copper homeostasis, particularly misregulation of loosely bound copper ions which are defined as the labile copper pool, occurs in major diseases such as cancer, where tumor growth and metastasis have a heightened requirement for this metal. To help decipher the role of copper in the etiology of cancer, we report a histochemical activity-based sensing approach that enables systematic, high-throughput profiling of labile copper status across many cell lines in parallel.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Health Sciences Institute of China Medical University, Shenyang 110122, China. Electronic address:
Recently study has found a new form of copper-dependent death called cuproptosis, which differs from apoptosis, ferroptosis, and necrosis. The main process of cuproptosis is copper directly combined with lipid-acetylated proteins in the TCA cycle of mitochondrial response, leading to the aggregation of lipid-acetylated proteins and the loss of Fe-S cluster proteins, resulting in mitochondrial dysfunction, and eventually causing cell death. Previous studies demonstrated that an imbalance in copper homeostasis exacerbates the pathological progression of Alzheimer's disease (AD) through the induction of oxidative stress, inflammatory response, and the accumulation of Aβ deposition and tau protein hyperphosphorylation.
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