Cuproptosis: mechanisms and links with cancers

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 7, 2023

Abstract Cuproptosis was a copper-dependent and unique kind of cell death that separate from existing other forms death. The last decade has witnessed considerable increase in investigations programmed death, whether copper induced an independent form long been argued until mechanism cuproptosis revealed. After that, increasing number researchers attempted to identify the relationship between process cancer. Thus, this review, we systematically detailed systemic cellular metabolic processes copper-related tumor signaling pathways. Moreover, not only focus on discovery its mechanism, but also outline association cancers. Finally, further highlight possible therapeutic direction employing ion ionophores with cuproptosis-inducing functions combination small molecule drugs for targeted therapy treat specific

Language: Английский

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Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: June 6, 2023

Cuproptosis and ferroptosis are the two newly defined metal-related regulated cell death. However, crosstalk between cuproptosis is obscure.We analyzed effect of inducers on copper ionophores-induced death through CCK-8 assay. was studied using immunofluorescence protein soluble-insoluble fraction isolation. GSH assay, qRT-PCR western blot were adopted to explore machinery enhanced cuproptosis. And mouse xenograft model built detect synergy elesclomol-Cu sorafenib in vivo.Herein we found that erastin could enhance primary liver cancer cells by increasing dependent lipoylated aggregation. Mechanically, upregulated lipoylation via suppressing mitochondrial matrix-related proteases mediated ferredoxin 1 (FDX1) degradation, reduced intracellular chelator glutathione (GSH) synthesis inhibiting cystine importing.Our findings proposed combination ionophores co-targeting be a novel therapeutic strategy for cancer.

Language: Английский

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Leveraging a disulfidptosis-based signature to improve the survival and drug sensitivity of bladder cancer patients

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 30, 2023

Background Disulfidptosis is a recently discovered form of cell death. However, its biological mechanisms in bladder cancer (BCa) are yet to be understood. Methods Disulfidptosis-related clusters were identified by consensus clustering. A disulfidptosis-related gene (DRG) prognostic model was established and verified various datasets. series experiments including qRT-PCR, immunoblotting, IHC, CCK-8, EdU, wound-healing, transwell, dual-luciferase reporter, ChIP assays used study the functions. Results We two DRG clusters, which exhibited distinct clinicopathological features, prognosis, tumor immune microenvironment (TIME) landscapes. with ten features (DCBLD2, JAM3, CSPG4, SCEL, GOLGA8A, CNTN1, APLP1, PTPRR, POU5F1, CTSE) several external datasets terms prognosis immunotherapy response prediction. BCa patients high scores may characterized declined survival, inflamed TIME, elevated mutation burden. Besides, correlation between score checkpoint genes chemoradiotherapy-related indicated implication personalized therapy. Furthermore, random survival forest analysis performed select top important within model: POU5F1 CTSE. immunohistochemistry showed enhanced expression CTSE tissues. phenotypic revealed oncogenetic roles cells. Mechanically, can transactivate CTSE, promoting proliferation metastasis. Conclusions Our highlighted disulfidptosis regulation progression, sensitivity therapy, patients. potential therapeutic targets for clinical treatment BCa.

Language: Английский

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Regulatory roles of copper metabolism and cuproptosis in human cancers

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: March 23, 2023

Copper is an essential micronutrient for human body and plays a vital role in various biological processes including cellular respiration free radical detoxification. Generally, copper metabolism the stable state, there are specific mechanisms to regulate maintain homeostasis. Dysregulation of may have great connection with types diseases, such as Wilson disease causing overload Menkes deficiency. Cancer presents high mortality rates world due unlimited proliferation potential, apoptosis escape immune properties induce organ failure. thought cancer, elevated levels cancer tissue serum. also affects tumor progression by affecting angiogenesis, metastasis other processes. Notably, cuproptosis novel form cell death that provide targeting strategies developing therapy. chelators ionophores two coordinating compounds treatment cancer. This review will explore relationship between cancers, clarify targeted

Language: Английский

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Copper Metabolism and Cuproptosis: Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases

Current Medical Science, Journal Year: 2024, Volume and Issue: 44(1), P. 28 - 50

Published: Feb. 1, 2024

Abstract Copper is an essential trace element, and plays a vital role in numerous physiological processes within the human body. During normal metabolism, body maintains copper homeostasis. deficiency or excess can adversely affect cellular function. Therefore, homeostasis stringently regulated. Recent studies suggest that trigger specific form of cell death, namely, cuproptosis, which triggered by excessive levels intracellular copper. Cuproptosis induces aggregation mitochondrial lipoylated proteins, loss iron-sulfur cluster proteins. In neurodegenerative diseases, pathogenesis progression neurological disorders are linked to This review summarizes advances cuproptosis nervous system diseases. offers research perspectives provide new insights into targeted treatment diseases based on cuproptosis.

Language: Английский

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Cuproptosis illustrates tumor micro-environment features and predicts prostate cancer therapeutic sensitivity and prognosis

Life Sciences, Journal Year: 2023, Volume and Issue: 325, P. 121659 - 121659

Published: April 1, 2023

Language: Английский

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Copper homeostasis and cuproptosis in tumor pathogenesis and therapeutic strategies

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 12, 2023

Copper is an indispensable micronutrient for the development and replication of all eukaryotes, its redox properties are both harmful beneficial to cells. An imbalance in copper homeostasis thought be involved carcinogenesis. Importantly, cancer cell proliferation, angiogenesis, metastasis cannot separated from effects copper. Cuproposis a copper-dependent form death that differs other existing modalities regulatory death. The role cuproptosis pathogenesis nervous cardiovascular systems has been widely studied; however, impact on malignant tumors yet fully understood clinical perspective. Exploring signaling pathways related will undoubtedly provide new perspective anti-tumor drugs future. Here, we systematically review systemic cellular metabolic processes mechanisms cancer. In addition, discuss possibility targeting ion prolong survival patients, with emphasis most representative ionophores chelators. We suggest attention should paid potential value treatment specific cancers.

Language: Английский

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Cuproptosis: emerging biomarkers and potential therapeutics in cancers

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Nov. 7, 2023

The sustenance of human life activities depends on copper, which also serves as a crucial factor for vital enzymes. Under typical circumstances, active homeostatic mechanisms keep the intracellular copper ion concentration low. Excess ions cause excessive cellular respiration, causes cytotoxicity and cell death levels steadily rise above threshold. It is novel that mitochondrial ions, regulation. Cuproptosis now understood to play role in several pathogenic processes, including inflammation, oxidative stress, apoptosis. Copper type regulatory death(RCD).Numerous diseases are correlated with development homeostasis imbalances. One most popular areas study field cancer cuproptosis. has been discovered angiogenesis, proliferation, growth, metastasis all accumulation ions. concentrations can serve marker development. In order reference clinical research product, diagnosis, treatment cancer, this paper covers function imbalance malignant cancers related molecular pathways.

Language: Английский

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Cuproptosis-a potential target for the treatment of osteoporosis

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: May 5, 2023

Osteoporosis is an age-related disease of bone metabolism marked by reduced mineral density and impaired strength. The causes the bones to weaken break more easily. Osteoclasts participate in resorption than osteoblasts formation, disrupting homeostasis leading osteoporosis. Currently, drug therapy for osteoporosis includes calcium supplements, vitamin D, parathyroid hormone, estrogen, calcitonin, bisphosphates, other medications. These medications are effective treating but have side effects. Copper a necessary trace element human body, studies shown that it links development Cuproptosis recently proposed new type cell death. Copper-induced death regulates lipoylated components mediated via mitochondrial ferredoxin 1; is, copper binds directly tricarboxylic acid cycle, resulting protein accumulation subsequent loss iron-sulfur cluster proteins, proteotoxic stress eventually Therapeutic options tumor disorders include targeting intracellular toxicity cuproptosis. hypoxic environment metabolic pathway glycolysis provide energy cells can inhibit cuproptosis, which may promote survival proliferation various cells, including osteoblasts, osteoclasts, effector T macrophages, thereby mediating process. As result, our group tried explain relationship between role cuproptosis its essential regulatory genes, as well pathological mechanism effects on cells. This study intends investigate treatment approach clinical beneficial

Language: Английский

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Novel insights into anticancer mechanisms of elesclomol: More than a prooxidant drug

Redox Biology, Journal Year: 2023, Volume and Issue: 67, P. 102891 - 102891

Published: Sept. 17, 2023

As an essential micronutrient for humans, the metabolism of copper is fine-tuned by evolutionarily conserved homeostatic mechanisms. Copper toxicity occurs when its concentration exceeds a certain threshold, which has been exploited in development ionophores, such as elesclomol, anticancer treatment. Elesclomol garnered recognition potent drug and evaluated numerous clinical trials. However, mechanisms underlying elesclomol-induced cell death remain obscure. The discovery cuproptosis, novel form triggered targeted accumulation mitochondria, redefines significance elesclomol cancer therapy. Here, we provide overview homeostasis associated pathological disorders, especially carcinogenesis. We summarize our current knowledge tumor suppressive with emphasis on cuproptosis. Finally, discuss strategies that may contribute to better application

Language: Английский

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