Research progress of copper death in tumor

doi:10.3760/cma.j.cn371439-20240727-00025

Abstract

Abstract:

Copper death is a newly discovered copper-dependent cell death mode that causes protein-toxic stress and triggers cell death by affecting mitochondrial tricarboxylic acid cycling and iron-sulfur tuftin loss. In recent years，with the in-depth study of the mechanism of copper death，it has been found that the genes related to copper death may be related to the clinical characteristics and prognosis of tumors，which can be used as potential biological targets for the diagnosis or treatment of tumors. At the same time，drugs targeting copper ions such as copper ionophores，copper chelators and copper containing complexes are widely studied. Further study on the mechanism of copper death in the development of tumor can provide new ideas for tumor diagnosis and treatment.

Key words: Neoplasms, Cell death, Copper death

Li Zhiyuan, Jia Xiuhong. Research progress of copper death in tumor[J]. Journal of International Oncology, 2025, 52(3): 163-168.

References 57

[1]	Porporato PE, Filigheddu N, Pedro JMB, et al. Mitochondrial metabolism and cancer[J]. Cell Res, 2018, 28(3): 265-280. DOI: 10.1038/cr.2017.155. pmid: 29219147
[2]	Tsvetkov P, Coy S, Petrova B, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins[J]. Science, 2022, 375(6586): 1254-1261. DOI: 10.1126/science.abf0529. pmid: 35298263
[3]	Ge EJ, Bush AI, Casini A, et al. Connecting copper and cancer: from transition metal signalling to metalloplasia[J]. Nat Rev Cancer, 2022, 22(2): 102-113. DOI: 10.1038/s41568-021-00417-2.
[4]	Cobine PA, Moore SA, Leary SC. Getting out what you put in: copper in mitochondria and its impacts on human disease[J]. Biochim Biophys Acta Mol Cell Res, 2021, 1868(1): 118867. DOI: 10.1016/j.bbamcr.2020.118867.
[5]	Tsvetkov P, Detappe A, Cai K, et al. Mitochondrial metabolism promotes adaptation to proteotoxic stress[J]. Nat Chem Biol, 2019, 15(7): 681-689. DOI: 10.1038/s41589-019-0291-9. pmid: 31133756
[6]	Liu H, Guo H, Jian Z, et al. Copper induces oxidative stress and apoptosis in the mouse liver[J]. Oxid Med Cell Longev, 2020, 2020: 1359164. DOI: 10.1155/2020/1359164.
[7]	Leal AS, Wang R, Salvador JA, et al. Semisynthetic ursolic acid fluorolactone derivatives inhibit growth with induction of p21(waf1) and induce apoptosis with upregulation of NOXA and downregulation of c-FLIP in cancer cells[J]. ChemMedChem, 2012, 7(9): 1635-1646. DOI: 10.1002/cmdc.201200282. pmid: 22807348
[8]	Lan Y, Bai P, Liu Y, et al. Visualization of receptor-interacting protein kinase 1 (RIPK1) by brain imaging with positron emission tomography[J]. J Med Chem, 2021, 64(20): 15420-15428. DOI: 10.1021/acs.jmedchem.1c01477. pmid: 34652135
[9]	Liao J, Hu Z, Li Q, et al. Endoplasmic reticulum stress contributes to copper-induced pyroptosis via regulating the IRE1α-XBP1 pathway in pig jejunal epithelial cells[J]. J Agric Food Chem, 2022, 70(4): 1293-1303. DOI: 10.1021/acs.jafc.1c07927.
[10]	Yang M, Wu X, Hu J, et al. COMMD10 inhibits HIF1α/CP loop to enhance ferroptosis and radiosensitivity by disrupting Cu-Fe balance in hepatocellular carcinoma[J]. J Hepatol, 2022, 76(5): 1138-1150. DOI: 10.1016/j.jhep.2022.01.009. pmid: 35101526
[11]	Wang X, Zhuang Y, Fang Y, et al. Endoplasmic reticulum stress aggravates copper-induced apoptosis via the PERK/ATF4/CHOP signaling pathway in duck renal tubular epithelial cells[J]. Environ Pollut, 2021, 272: 115981. DOI: 10.1016/j.envpol.2020.115981.
[12]	Wu H, Guo H, Liu H, et al. Copper sulfate-induced endoplasmic reticulum stress promotes hepatic apoptosis by activating CHOP, JNK and caspase-12 signaling pathways[J]. Ecotoxicol Environ Saf, 2020, 191: 110236. DOI: 10.1016/j.ecoenv.2020.110236.
[13]	Chen X, Zhang X, Chen J, et al. Hinokitiol copper complex inhibits proteasomal deubiquitination and induces paraptosis-like cell death in human cancer cells[J]. Eur J Pharmacol, 2017, 815: 147-155. DOI: 10.1016/j.ejphar.2017.09.003. pmid: 28887042
[14]	Pilankar A, Singhavi H, Raghuram GV, et al. A pro-oxidant combination of resveratrol and copper down-regulates hallmarks of cancer and immune checkpoints in patients with advanced oral cancer: results of an exploratory study (RESCU 004)[J]. Front Oncol, 2022, 12: 1000957. DOI: 10.3389/fonc.2022.1000957.
[15]	Yang W, Wang Y, Huang Y, et al. 4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH to promote cuproptosis in colorectal cancer[J]. Biomed Pharmacother, 2023, 159: 114301. DOI: 10.1016/j.biopha.2023.114301.
[16]	Geng R, Ke N, Wang Z, et al. Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition[J]. Chem Biol Interact, 2023, 382: 110546. DOI: 10.1016/j.cbi.2023.110546.
[17]	Zhang Z, Ma Y, Guo X, et al. FDX1 can impact the prognosis and mediate the metabolism of lung adenocarcinoma[J]. Front Pharmacol, 2021, 12: 749134. DOI: 10.3389/fphar.2021.749134.
[18]	Chen G, Zhang J, Teng W, et al. FDX1 inhibits thyroid cancer malignant progression by inducing cuprotosis[J]. Heliyon, 2023, 9(8): e18655. DOI: 10.1016/j.heliyon.2023.e18655.
[19]	Zhang C, Zeng Y, Guo X, et al. Pan-cancer analyses confirmed the cuproptosis-related gene FDX1 as an immunotherapy predictor and prognostic biomarker[J]. Front Genet, 2022, 13: 923737. DOI: 10.3389/fgene.2022.923737.
[20]	Sun L, Zhang Y, Yang B, et al. Lactylation of METTL16 promotes cuproptosis via m⁶A-modification on FDX1 mRNA in gastric cancer[J]. Nat Commun, 2023, 14(1): 6523. DOI: 10.1038/s41467-023-42025-8.
[21]	Zhao F, Hao Z, Zhong Y, et al. Discovery of breast cancer risk genes and establishment of a prediction model based on estrogen metabolism regulation[J]. BMC Cancer, 2021, 21(1): 194. DOI: 10.1186/s12885-021-07896-4. pmid: 33632172
[22]	Ke H, Suzuki A, Miyamoto T, et al. 4-Hydroxy estrogen induces DNA damage on codon 130/131 of PTEN in endometrial carcinoma cells[J]. Mol Cell Endocrinol, 2015, 400: 71-77. DOI: 10.1016/j.mce.2014.10.027. pmid: 25449419
[23]	Zhao J, Guo S, Schrodi SJ, et al. Cuproptosis and cuproptosis-related genes in rheumatoid arthritis: implication, prospects, and perspectives[J]. Front Immunol, 2022, 13: 930278. DOI: 10.3389/fimmu.2022.930278.
[24]	Cai Y, He Q, Liu W, et al. Comprehensive analysis of the potential cuproptosis-related biomarker LIAS that regulates prognosis and immunotherapy of pan-cancers[J]. Front Oncol, 2022, 12: 952129. DOI: 10.3389/fonc.2022.952129.
[25]	Raggi C, Taddei ML, Sacco E, et al. Mitochondrial oxidative metabolism contributes to a cancer stem cell phenotype in cholangiocarcinoma[J]. J Hepatol, 2021, 74(6): 1373-1385. DOI: 10.1016/j.jhep.2020.12.031. pmid: 33484774
[26]	Zhao Y, Xu G, Li H, et al. Overexpression of endogenous lipoic acid synthase attenuates pulmonary fibrosis induced by crystalline silica in mice[J]. Toxicol Lett, 2020, 323: 57-66. DOI: 10.1016/j.toxlet.2020.01.023. pmid: 32017981
[27]	Chen Y. Identification and validation of cuproptosis-related prognostic signature and associated regulatory axis in uterine corpus endometrial carcinoma[J]. Front Genet, 2022, 13: 912037. DOI: 10.3389/fgene.2022.912037.
[28]	Yan C, Niu Y, Ma L, et al. System analysis based on the cuproptosis-related genes identifies LIPT1 as a novel therapy target for liver hepatocellular carcinoma[J]. J Transl Med, 2022, 20(1): 452. DOI: 10.1186/s12967-022-03630-1. pmid: 36195876
[29]	Peng Y, Shi R, Yang S, et al. Cuproptosis-related gene DLAT is a biomarker of the prognosis and immune microenvironment of gastric cancer and affects the invasion and migration of cells[J]. Cancer Med, 2024, 13(14): e70012. DOI: 10.1002/cam4.70012.
[30]	Chen Q, Wang Y, Yang L, et al. PM2.5 promotes NSCLC carcinogenesis through translationally and transcriptionally activating DLAT-mediated glycolysis reprograming[J]. J Exp Clin Cancer Res, 2022, 41(1): 229. DOI: 10.1186/s13046-022-02437-8. pmid: 35869499
[31]	Zhang C, Xu T, Ji K, et al. An integrative analysis reveals the prognostic value and potential functions of PSMD11 in hepatocellular carcinoma[J]. Mol Carcinog, 2023, 62(9): 1355-1368. DOI: 10.1002/mc.23568.
[32]	Ye Z, Zhang S, Cai J, et al. Development and validation of cuproptosis-associated prognostic signatures in WHO 2/3 glioma[J]. Front Oncol, 2022, 12: 967159. DOI: 10.3389/fonc.2022.967159.
[33]	Liu H. Pan-cancer profiles of the cuproptosis gene set[J]. Am J Cancer Res, 2022, 12(8): 4074-4081. pmid: 36119826
[34]	Zhao L, Geng R, Huang Y, et al. AP2α negatively regulates PDHA1 in cervical cancer cells to promote aggressive features and aerobic glycolysis in vitro and in vivo[J]. J Gynecol Oncol, 2023, 34(5): e59. DOI: 10.3802/jgo.2023.34.e59.
[35]	Deng L, Jiang A, Zeng H, et al. Comprehensive analyses of PDHA1 that serves as a predictive biomarker for immunotherapy response in cancer[J]. Front Pharmacol, 2022, 13: 947372. DOI: 10.3389/fphar.2022.947372.
[36]	Giannos P, Kechagias KS, Gal A. Identification of prognostic gene biomarkers in non-small cell lung cancer progression by integrated bioinformatics analysis[J]. Biology (Basel), 2021, 10(11): 1200. DOI: 10.3390/biology10111200.
[37]	Wu J, Wang S, Liu Y, et al. Integrated single-cell and bulk characterization of cuproptosis key regulator PDHB and association with tumor microenvironment infiltration in clear cell renal cell carcinoma[J]. Front Immunol, 2023, 14: 1132661. DOI: 10.3389/fimmu.2023.1132661.
[38]	Yang C, Lee D, Zhang MS, et al. Genome-wide CRISPR/Cas9 library screening revealed dietary restriction of glutamine in combination with inhibition of pyruvate metabolism as effective liver cancer treatment[J]. Adv Sci (Weinh), 2022, 9(34): e2202104. DOI: 10.1002/advs.202202104.
[39]	McCann C, Quinteros M, Adelugba I, et al. The mitochondrial Cu⁺ transporter PiC2 (slc25a3) is a target of MTF1 and contributes to the development of skeletal muscle in vitro[J]. Front Mol Biosci, 2022, 9: 1037941. DOI: 10.3389/fmolb.2022.1037941.
[40]	Zhao S, Chen S, Liu W, et al. Integrated machine learning and bioinformatic analyses used to construct a copper-induced cell death-related classifier for prognosis and immunotherapeutic response of hepatocellular carcinoma patients[J]. Front Pharmacol, 2023, 14: 1188725. DOI: 10.3389/fphar.2023.1188725.
[41]	Fan K, Dong Y, Li T, et al. Cuproptosis-associated CDKN2A is targeted by plicamycin to regulate the microenvironment in patients with head and neck squamous cell carcinoma[J]. Front Genet, 2023, 13: 1036408. DOI: 10.3389/fgene.2022.1036408.
[42]	Zeng M, Wu B, Wei W, et al. Disulfiram: a novel repurposed drug for cancer therapy[J]. Chin Med J (Engl), 2024, 137(12): 1389-1398. DOI: 10.1097/cm9.0000000000002909.
[43]	Kang X, Jadhav S, Annaji M, et al. Advancing cancer therapy with copper/disulfiram nanomedicines and drug delivery systems[J]. Pharmaceutics, 2023, 15(6): 1567. DOI: 10.3390/pharmaceutics15061567.
[44]	Yang Y, Deng Q, Feng X, et al. Use of the disulfiram/copper complex for breast cancer chemoprevention in MMTV-erbB2 transgenic mice[J]. Mol Med Rep, 2015, 12(1): 746-752. DOI: 10.3892/mmr.2015.3426. pmid: 25738885
[45]	Skrott Z, Majera D, Gursky J, et al. Disulfiram's anti-cancer activity reflects targeting NPL4, not inhibition of aldehyde dehydrogenase[J]. Oncogene, 2019, 38(40): 6711-6722. DOI: 10.1038/s41388-019-0915-2. pmid: 31391554
[46]	Kang X, Wang J, Huang CH, et al. Diethyldithiocarbamate copper nanoparticle overcomes resistance in cancer therapy without inhibiting P-glycoprotein[J]. Nanomedicine, 2023, 47: 102620. DOI: 10.1016/j.nano.2022.102620.
[47]	Zheng P, Zhou C, Lu L, et al. Elesclomol: a copper ionophore targeting mitochondrial metabolism for cancer therapy[J]. J Exp Clin Cancer Res, 2022, 41(1): 271. DOI: 10.1186/s13046-022-02485-0. pmid: 36089608
[48]	Bristot IJ, Kehl Dias C, Chapola H, et al. Metabolic rewiring in melanoma drug-resistant cells[J]. Crit Rev Oncol Hematol, 2020, 153: 102995. DOI: 10.1016/j.critrevonc.2020.102995.
[49]	Liu H, Zhang Y, Zheng S, et al. Detention of copper by sulfur nanoparticles inhibits the proliferation of A375 malignant melanoma and MCF-7 breast cancer cells[J]. Biochem Biophys Res Commun, 2016, 477(4): 1031-1037. DOI: 10.1016/j.bbrc.2016.07.026.
[50]	Ramchandani D, Berisa M, Tavarez DA, et al. Copper depletion modulates mitochondrial oxidative phosphorylation to impair triple negative breast cancer metastasis[J]. Nat Commun, 2021, 12(1): 7311. DOI: 10.1038/s41467-021-27559-z. pmid: 34911956
[51]	Kim YJ, Tsang T, Anderson GR, et al. Inhibition of BCL2 family members increases the efficacy of copper chelation in BRAF^V600E-driven melanoma[J]. Cancer Res, 2020, 80(7): 1387-1400. DOI: 10.1158/0008-5472.Can-19-1784.
[52]	Xue Q, Kang R, Klionsky DJ, et al. Copper metabolism in cell death and autophagy[J]. Autophagy, 2023, 19(8): 2175-2195. DOI: 10.1080/15548627.2023.2200554.
[53]	Voli F, Valli E, Lerra L, et al. Intratumoral copper modulates PD-L1 expression and influences tumor immune evasion[J]. Cancer Res, 2020, 80(19): 4129-4144. DOI: 10.1158/0008-5472.CAN-20-0471. pmid: 32816860
[54]	Yang Y, Liang S, Geng H, et al. Proteomics revealed the crosstalk between copper stress and cuproptosis, and explored the feasibility of curcumin as anticancer copper ionophore[J]. Free Radic Biol Med, 2022, 193(Pt 2): 638-647. DOI: 10.1016/j.freeradbiomed.2022.11.023.
[55]	Kordestani N, Rudbari HA, Fernandes AR, et al. Antiproliferative activities of diimine-based mixed ligand copper(Ⅱ) complexes[J]. ACS Comb Sci, 2020, 22(2): 89-99. DOI: 10.1021/acscombsci.9b00202. pmid: 31913012
[56]	Luo B, Chen L, Hong Z, et al. A simple and feasible atom-precise biotinylated Cu(Ⅰ) complex for tumor-targeted chemodynamic therapy[J]. Chem Commun (Camb), 2021, 57(49): 6046-6049. DOI: 10.1039/d1cc00515d.
[57]	Wang J, Xu M, Wang D, et al. Copper-doped carbon dots for optical bioimaging and photodynamic therapy[J]. Inorg Chem, 2019, 58(19): 13394-13402. DOI: 10.1021/acs.inorgchem.9b02283. pmid: 31556604