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铜死亡：一项治疗肿瘤的新途径
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Abstract:
铜离子导致细胞死亡是一种铜依赖性且独特的细胞死亡，与其他现有的形式的细胞死亡不同。长期以来，铜诱导的细胞死亡是否可以导致细胞死亡及其导致细胞死亡的机制一直存在争议，直到最近的研究铜死亡cuproptosis的机制被发现。在那之后，越来越多的研究人员试图确定cuproptosis与癌症过程之间的关系。因此，在这篇综述中，我们系统地详细介绍了铜离子在人类的全身和细胞代谢过程，以及铜离子在肿瘤中的作用。其次，讲明了cuproptosis的发现过程及其机制，还概述了cuproptosis及其关键基因FDX1与癌症之间的关联，及FDX1与现有的肿瘤药物相互作用的新进展。
Cell death caused by copper ions is a copper-dependent and unique cell death that is different from other existing forms of cell death. For a long time, whether copper-induced cell death can lead to cell death and the mechanism by which it leads to cell death have been controversial until recent studies have discovered the mechanism of copper death cuproptosis. Since then, more and more researchers have tried to determine the relationship between cuproptosis and cancer processes. Therefore, in this review, we systematically and in detail introduce the systemic and cellular metabolic processes of copper ions in humans, as well as the role of copper ions in tumors. Secondly, the discovery process and mechanism of cuproptosis are explained, and the association between cuproptosis and its key gene FDX1 and cancer is also outlined, as well as new progress in the interaction between FDX1 and existing tumor drugs.
| [1] | Tang, D., Kang, R., Berghe, T.V., Vandenabeele, P. and Kroemer, G. (2019) The Molecular Machinery of Regulated Cell Death. Cell Research, 29, 347-364. https://doi.org/10.1038/s41422-019-0164-5 |
| [2] | Tang, D., Chen, X. and Kroemer, G. (2022) Cuproptosis: A Copper-Triggered Modality of Mitochondrial Cell Death. Cell Research, 32, 417-418. https://doi.org/10.1038/s41422-022-00653-7 |
| [3] | Cobine, P.A. and Brady, D.C. (2022) Cuproptosis: Cellular and Molecular Mechanisms Underlying Copper-Induced Cell Death. Molecular Cell, 82, 1786-1787. https://doi.org/10.1016/j.molcel.2022.05.001 |
| [4] | Yang, F., Pei, R., Zhang, Z., et.al. (2019) Copper Induces Oxidative Stress and Apoptosis through Mitochondria-Mediated Pathway in Chicken Hepatocytes. Toxicology in Vitro, 54, 310-316. https://doi.org/10.1016/j.tiv.2018.10.017 |
| [5] | Que, E.L., Domaille, D.W. and Chang, C.J. (2008) Metals in Neurobiology: Probing Their Chemistry and Biology with Molecular Imaging. Chemical Reviews, 108, 1517-1549. https://doi.org/10.1021/cr078203u |
| [6] | Prohaska, J.R. (2012) Copper. In: Erdman Jr, J.W., Macdonald, I.A. and Zeisel, S.H., Eds., Present Knowledge in Nutrition, Wiley-Blackwell, 540-553 |
| [7] | Wang, Y., Zhu, S., Hodgkinson, V., Prohaska, J.R., Weisman, G.A., Gitlin, J.D., et al. (2012) Maternofetal and Neonatal Copper Requirements Revealed by Enterocyte-Specific Deletion of the Menkes Disease Protein. American Journal of Physiology-Gastrointestinal and Liver Physiology, 303, G1236-G1244. https://doi.org/10.1152/ajpgi.00339.2012 |
| [8] | Kirsipuu, T., Zadorožnaja, A., Smirnova, J., Friedemann, M., Plitz, T., Tõugu, V., et al. (2020) Copper(II)-Binding Equilibria in Human Blood. Scientific Reports, 10, Article No. 5686. https://doi.org/10.1038/s41598-020-62560-4 |
| [9] | Hernandez, S., Tsuchiya, Y., García-Ruiz, J.P., Lalioti, V., Nielsen, S., Cassio, D., et al. (2008) ATP7B Copper-Regulated Traffic and Association with the Tight Junctions: Copper Excretion into the Bile. Gastroenterology, 134, 1215-1223. https://doi.org/10.1053/j.gastro.2008.01.043 |
| [10] | Lutsenko, S. (2021) Dynamic and Cell-Specific Transport Networks for Intracellular Copper Ions. Journal of Cell Science, 134, jcs240523. https://doi.org/10.1242/jcs.240523 |
| [11] | Denoyer, D., Masaldan, S., La Fontaine, S. and Cater, M.A. (2015) Targeting Copper in Cancer Therapy: ‘Copper That Cancer’. Metallomics, 7, 1459-1476. https://doi.org/10.1039/c5mt00149h |
| [12] | Lopez, J., Ramchandani, D. and Vahdat, L. (2019) 12. Copper Depletion as a Therapeutic Strategy in Cancer. In: Carver, P.L., Ed., Essential Metals in Medicine: Therapeutic Use and Toxicity of Metal Ions in the Clinic, De Gruyter, 303-330. https://doi.org/10.1515/9783110527872-012 |
| [13] | Ge, E.J., Bush, A.I., Casini, A., Cobine, P.A., Cross, J.R., DeNicola, G.M., et al. (2021) Connecting Copper and Cancer: From Transition Metal Signalling to Metalloplasia. Nature Reviews Cancer, 22, 102-113. https://doi.org/10.1038/s41568-021-00417-2 |
| [14] | Shanbhag, V., Jasmer-McDonald, K., Zhu, S., et al. (2019) ATP7A Delivers Copper to the Lysyl Oxidase Family of Enzymes and Promotes Tumorigenesis and Metastasis. Proceedings of the National Academy of Sciences, 116, 6836-6841. https://doi.org/10.1073/pnas.1817473116 |
| [15] | Krishnamoorthy, L., Cotruvo, J.A., Chan, J., Kaluarachchi, H., Muchenditsi, A., Pendyala, V.S., et al. (2016) Copper Regulates Cyclic-AMP-Dependent Lipolysis. Nature Chemical Biology, 12, 586-592. https://doi.org/10.1038/nchembio.2098 |
| [16] | Brady, D.C., Crowe, M.S., Turski, M.L., Hobbs, G.A., Yao, X., Chaikuad, A., et al. (2014) Copper Is Required for Oncogenic BRAF Signalling and Tumorigenesis. Nature, 509, 492-496. https://doi.org/10.1038/nature13180 |
| [17] | Halliwell, B. and Gutteridge, J.M.C. (1984) Oxygen Toxicity, Oxygen Radicals, Transition Metals and Disease. Biochemical Journal, 219, 1-14. https://doi.org/10.1042/bj2190001 |
| [18] | Nagai, M., Vo, N.H., Shin Ogawa, L., Chimmanamada, D., Inoue, T., Chu, J., et al. (2012) The Oncology Drug Elesclomol Selectively Transports Copper to the Mitochondria to Induce Oxidative Stress in Cancer Cells. Free Radical Biology and Medicine, 52, 2142-2150. https://doi.org/10.1016/j.freeradbiomed.2012.03.017 |
| [19] | Yadav, A.A., Patel, D., Wu, X. and Hasinoff, B.B. (2013) Molecular Mechanisms of the Biological Activity of the Anticancer Drug Elesclomol and Its Complexes with Cu(II), Ni(II) and Pt(II). Journal of Inorganic Biochemistry, 126, 1-6. https://doi.org/10.1016/j.jinorgbio.2013.04.013 |
| [20] | Oliveri, V. (2022) Selective Targeting of Cancer Cells by Copper Ionophores: An Overview. Frontiers in Molecular Biosciences, 9, Article 841814. https://doi.org/10.3389/fmolb.2022.841814 |
| [21] | Cen, D., Brayton, D., Shahandeh, B., et al. (2004) Disulfiram Facilitates Intracellular Cu Uptake and Induces Apoptosis in Human Melanoma Cells. Journal of Medicinal Chemistry, 47, 6914-6920. https://doi.org/10.1021/jm049568z |
| [22] | Kirshner, J.R., He, S., Balasubramanyam, V., Kepros, J., Yang, C., Zhang, M., et al. (2008) Elesclomol Induces Cancer Cell Apoptosis through Oxidative Stress. Molecular Cancer Therapeutics, 7, 2319-2327. https://doi.org/10.1158/1535-7163.mct-08-0298 |
| [23] | Tsvetkov, P., Coy, S., Petrova, B., Dreishpoon, M., Verma, A., Abdusamad, M., et al. (2022) Copper Induces Cell Death by Targeting Lipoylated TCA Cycle Proteins. Science, 375, 1254-1261. https://doi.org/10.1126/science.abf0529 |
| [24] | Rowland, E.A., Snowden, C.K. and Cristea, I.M. (2018) Protein Lipoylation: An Evolutionarily Conserved Metabolic Regulator of Health and Disease. Current Opinion in Chemical Biology, 42, 76-85. https://doi.org/10.1016/j.cbpa.2017.11.003 |
| [25] | Tang, Q., Guo, Y., Meng, L. and Chen, X. (2020) Chemical Tagging of Protein Lipoylation. Angewandte Chemie International Edition, 60, 4028-4033. https://doi.org/10.1002/anie.202010981 |
| [26] | Solmonson, A. and DeBerardinis, R.J. (2018) Lipoic Acid Metabolism and Mitochondrial Redox Regulation. Journal of Biological Chemistry, 293, 7522-7530. https://doi.org/10.1074/jbc.tm117.000259 |
| [27] | Przybyla-Toscano, J., Maclean, A.E., Franceschetti, M., Liebsch, D., Vignols, F., Keech, O., et al. (2021) Protein Lipoylation in Mitochondria Requires Fe-S Cluster Assembly Factors NFU4 and NFU5. Plant Physiology, 188, 997-1013. https://doi.org/10.1093/plphys/kiab501 |
| [28] | Cai, K., Tonelli, M., Frederick, R.O. and Markley, J.L. (2017) Human Mitochondrial Ferredoxin 1 (FDX1) and Ferredoxin 2 (FDX2) Both Bind Cysteine Desulfurase and Donate Electrons for Iron-Sulfur Cluster Biosynthesis. Biochemistry, 56, 487-499. https://doi.org/10.1021/acs.biochem.6b00447 |
| [29] | Sheftel, A.D., Stehling, O., Pierik, A.J., Elsässer, H., Mühlenhoff, U., Webert, H., et al. (2010) Humans Possess Two Mitochondrial Ferredoxins, FDX1 and FDX2, with Distinct Roles in Steroidogenesis, Heme, and Fe/S Cluster Biosynthesis. Proceedings of the National Academy of Sciences, 107, 11775-11780. https://doi.org/10.1073/pnas.1004250107 |
| [30] | Shi, Y., Ghosh, M., Kovtunovych, G., Crooks, D.R. and Rouault, T.A. (2012) Both Human Ferredoxins 1 and 2 and Ferredoxin Reductase Are Important for Iron-Sulfur Cluster Biogenesis. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1823, 484-492. https://doi.org/10.1016/j.bbamcr.2011.11.002 |
| [31] | Arroyo, J.D., Jourdain, A.A., Calvo, S.E., Ballarano, C.A., Doench, J.G., Root, D.E., et al. (2016) A Genome-Wide CRISPR Death Screen Identifies Genes Essential for Oxidative Phosphorylation. Cell Metabolism, 24, 875-885. https://doi.org/10.1016/j.cmet.2016.08.017 |
| [32] | Lu, H., Liang, J., He, X., Ye, H., Ruan, C., Shao, H., et al. (2023) A Novel Oncogenic Role of FDX1 in Human Melanoma Related to PD-L1 Immune Checkpoint. International Journal of Molecular Sciences, 24, Article 9182. https://doi.org/10.3390/ijms24119182 |
| [33] | Wang, Y., Zhang, X., Chen, G., Xing, Q., Zhu, B. and Wang, X. (2023) Integrated Analyses Reveal the Prognostic, Immunological Features and Mechanisms of Cuproptosis Critical Mediator Gene FDX1 in KIRC. Genes & Immunity, 24, 171-182. https://doi.org/10.1038/s41435-023-00211-0 |
| [34] | Schaafsma, E., Fugle, C.M., Wang, X. and Cheng, C. (2021) Pan-Cancer Association of HLA Gene Expression with Cancer Prognosis and Immunotherapy Efficacy. British Journal of Cancer, 125, 422-432. https://doi.org/10.1038/s41416-021-01400-2 |
| [35] | Liu, Z. and Miao, J. (2023) Prognostic and Immunological Role of FDX1 in Pan-Cancer: An in-Silico Analysis. Scientific Reports, 13, Article No. 7926. https://doi.org/10.1038/s41598-023-34752-1 |
| [36] | Xiao, C., Yang, L., Jin, L., Lin, W., Zhang, F., Huang, S., et al. (2022) Prognostic and Immunological Role of Cuproptosis-Related Protein FDX1 in Pan-Cancer. Frontiers in Genetics, 13, Article 962028. https://doi.org/10.3389/fgene.2022.962028 |
| [37] | Yang, L., Zhang, Y., Wang, Y., et al. (2022) Ferredoxin 1 Is a Cuproptosis-Key Gene Responsible for Tumor Immunity and Drug Sensitivity: A Pan-Cancer Analysis. Frontiers in Pharmacology, 13, Article 938134. https://doi.org/10.3389/fphar.2022.938134 |
| [38] | Picard, E., Verschoor, C.P., Ma, G.W. and Pawelec, G. (2020) Relationships between Immune Landscapes, Genetic Subtypes and Responses to Immunotherapy in Colorectal Cancer. Frontiers in Immunology, 11, Article 369. https://doi.org/10.3389/fimmu.2020.00369 |
| [39] | Zhang, C., Zeng, Y., Guo, X., Shen, H., Zhang, J., Wang, K., et al. (2022) Pan-Cancer Analyses Confirmed the Cuproptosis-Related Gene FDX1 as an Immunotherapy Predictor and Prognostic Biomarker. Frontiers in Genetics, 13, Article 923737. https://doi.org/10.3389/fgene.2022.923737 |
| [40] | Ashton, T.M., McKenna, W.G., Kunz-Schughart, L.A., et al. (2018) Oxidative Phosphorylation as an Emerging Target in Cancer Therapy. Clinical Cancer Research, 24, 2482-2490. https://doi.org/10.1158/1078-0432.CCR-17-3070 |
| [41] | Wang, L., Cao, Y., Guo, W. and Xu, J. (2022) High Expression of Cuproptosis-Related Gene FDX1 in Relation to Good Prognosis and Immune Cells Infiltration in Colon Adenocarcinoma (COAD). Journal of Cancer Research and Clinical Oncology, 149, 15-24. https://doi.org/10.1007/s00432-022-04382-7 |
| [42] | Chen, G., Zhang, J., Teng, W., Luo, Y. and Ji, X. (2023) FDX1 Inhibits Thyroid Cancer Malignant Progression by Inducing Cuprotosis. Heliyon, 9, e18655. https://doi.org/10.1016/j.heliyon.2023.e18655 |
| [43] | Takahashi, R., Kamizaki, K., Yamanaka, K., Terai, Y. and Minami, Y. (2023) Expression of Ferredoxin1 in Cisplatin-Resistant Ovarian Cancer Cells Confers Their Resistance against Ferroptosis Induced by Cisplatin. Oncology Reports, 49, Article No. 124. https://doi.org/10.3892/or.2023.8561 |
| [44] | Quan, B., Liu, W., Yao, F., et al. (2023) LINC02362/hsa-miR-18a-5p/FDX1 Axis Suppresses Proliferation and Drives Cuproptosis and Oxaliplatin Sensitivity of Hepatocellular Carcinoma. American Journal of Cancer Research, 13, 5590-5609. |
