Dihydrolipoamide dehydrogenase promotes hepatocellular carcinoma progression and modulates cuproptosis-dependent cell death

Abraham Gnanadass S, Pandey S, Viswanathan P (2025) Decoding cuproptosis and cuproplasia: implications for therapeutic strategies in renal cell carcinoma. Cell Death Discov 11:501. https://doi.org/10.1038/s41420-025-02734-z

Article  PubMed  PubMed Central  CAS  Google Scholar 

Anjana V, Anand S, Thakur P, Pal R, Acharjee S, Singh R, Sharma S, Kumawat M, Tomar RS (2025) Copper Homeostasis at the Crossroads of Cellular Metabolism, Epigenetic Regulation and Protein Trafficking. Traffic 26:e70024. https://doi.org/10.1111/tra.70024

Article  PubMed  CAS  Google Scholar 

Boaru DL, Leon-Oliva D, Castro-Martinez P, Garcia-Montero C, Fraile-Martinez O, Garcia-Gonzalez B, Perez-Gonzalez I, Michael Alhaddadin MN, Barrena-Blazquez S, Lopez-Gonzalez L, la Torre B, Guijarro LG, Pekarek L, Saez MA, Rios-Espinosa L, Garrido-Gil MJ, Gimeno-Longas MJ, Pekarek T, Diaz-Pedrero R, Alvarez-Mon M, Ortega MA (2025) Cuproptosis: Current insights into its multifaceted role in disease, cancer, and translational/therapeutic opportunities. Biomed Pharmacother 190:118422. https://doi.org/10.1016/j.biopha.2025.118422

Article  PubMed  CAS  Google Scholar 

Cui PP, Yang QC, Sun ZJ (2026) Targeting cuproptosis with nanomaterials for cancer immunotherapy. Acta Biomater 209:38–63. https://doi.org/10.1016/j.actbio.2025.11.028

Article  PubMed  CAS  Google Scholar 

Guo K, Wang T, Yin J, Yang S, Cui H, Cao Z, Zhao Q, Xie G, Lu J, Gu G, Wu W (2024) Identification of Cuproptosis-Related Patterns Predict Prognosis and Immunotherapy Response in Hepatocellular Carcinoma. J Cell Mol Med 28:e70224. https://doi.org/10.1111/jcmm.70224

Article  PubMed  PubMed Central  CAS  Google Scholar 

Hsiao JC, Warui DM, Kwon JJ, Dreishpoon MB, Bick NR, Blue-Lahom T, Root DE, Booker SJ, Tsvetkov P (2025) Deep Mutational Scanning of FDX1 Identifies Key Structural Determinants of Lipoylation and Cuproptosis. Nat Commun. https://doi.org/10.1038/s41467-025-67869-0

Article  PubMed  PubMed Central  Google Scholar 

Jiang D, Zhuang L, Koong AC, Gan B (2025a) Cuproptosis in cancer: from molecular mechanisms to therapeutic intervention. Trends Cancer DOI. https://doi.org/10.1016/j.trecan.2025.12.002

Article  Google Scholar 

Jiang Z, Dai J, Jiang J, Deng S, Gu J, Wang J, Chen M, Cai W, Wu K, Tao K, Liu K, Cai K (2025b) Engineering Inorganic Nanoparticles to Induce Cuproptosis: A New Strategy for Cancer Therapy. Pharmaceutics 17. https://doi.org/10.3390/pharmaceutics17111383

Li SR, Bu LL, Cai L (2022) Cuproptosis: lipoylated TCA cycle proteins-mediated novel cell death pathway. Signal Transduct Target Ther 7:158. https://doi.org/10.1038/s41392-022-01014-x

Article  PubMed  PubMed Central  CAS  Google Scholar 

Li X, Li L, He N, Kou D, Chen S, Song H, Yan X (2024a) Pathomics signatures and cuproptosis-related genes signatures for prediction of prognosis in patients with hepatocellular carcinoma. Transl Cancer Res 13:5473–5483. https://doi.org/10.21037/tcr-24-350

Article  PubMed  PubMed Central  CAS  Google Scholar 

Li X, Rui J, Yang Z, Shang-Guan F, Shi H, Wang D, Sun J (2024b) Cuproptosis Related Gene DLD Associated with Poor Prognosis and Malignant Biological Characteristics in Lung Adenocarcinoma. Curr Cancer Drug Targets 24:867–880. https://doi.org/10.2174/0115680096271679231213060750

Article  PubMed  CAS  Google Scholar 

Lin J, Wang G, Cheng S, Hu Y, Li H, Feng W, Liu X, Xu C (2023) Pan-Cancer Analysis of the Cuproptosis-Related Gene DLD. Mediators Inflamm 2023:5533444. https://doi.org/10.1155/2023/5533444

Article  PubMed  PubMed Central  CAS  Google Scholar 

Lin K, Cai J, Pan S, Yu X, Qiu Y, Ying Z, Feng H, Zhang L, Liu Y, Shen H, Hong Y, Li Q, Jin R (2024) Screening of PDSS1 as a Potential Biomarker for Hepatocellular Carcinoma Based on a Copper-Related Prognostic Signature through Bulk and Single-cell RNA-sequencing Analysis. J Cancer 15:5028–5045. https://doi.org/10.7150/jca.96867

Article  PubMed  PubMed Central  CAS  Google Scholar 

Liu H (2022) Pan-cancer profiles of the cuproptosis gene set. Am J Cancer Res 12:4074–4081

PubMed  PubMed Central  CAS  Google Scholar 

Liu C, Fang Z, Yang K, Ji Y, Yu X, Guo Z, Dong Z, Zhu T, Liu C (2024) Identification and validation of cuproptosis-related molecular clusters in non-alcoholic fatty liver disease. J Cell Mol Med 28:e18091. https://doi.org/10.1111/jcmm.18091

Article  PubMed  PubMed Central  CAS  Google Scholar 

Liu X, Qu H, Li J, Sun X, Wang Z, Wang D, Bai X, Li X (2025) p53 enhances elesclomol-Cu-induced cuproptosis in hepatocellular carcinoma via FDXR-mediated FDX1 upregulation. Front Oncol 15:1584811. https://doi.org/10.3389/fonc.2025.1584811

Article  PubMed  PubMed Central  CAS  Google Scholar 

Nagai M, Vo NH, Shin Ogawa L, Chimmanamada D, Inoue T, Chu J, Beaudette-Zlatanova BC, Lu R, Blackman RK, Barsoum J, Koya K, Wada Y (2012) The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells. Free Radic Biol Med 52:2142–2150. https://doi.org/10.1016/j.freeradbiomed.2012.03.017

Article  PubMed  CAS  Google Scholar 

Skerlova J, Berndtsson J, Nolte H, Ott M, Stenmark P (2021) Structure of the native pyruvate dehydrogenase complex reveals the mechanism of substrate insertion. Nat Commun 12:5277. https://doi.org/10.1038/s41467-021-25570-y

Article  PubMed  PubMed Central  CAS  Google Scholar 

Solmonson A, DeBerardinis RJ (2018) Lipoic acid metabolism and mitochondrial redox regulation. J Biol Chem 293:7522–7530. https://doi.org/10.1074/jbc.TM117.000259

Article  PubMed  CAS  Google Scholar 

Wang Y, Zhou M, Lan J, Hu T, Wang T, Zuo C (2025) Copper homeostasis and its dysregulation in diseases: A focus on cuproptosis. Chem Biol Interact 424:111879. https://doi.org/10.1016/j.cbi.2025.111879

Article  PubMed  CAS  Google Scholar 

Wu C, Liu X, Zhong L, Zhou Y, Long L, Yi T, Chen S, Li Y, Chen Y, Shen L, Zeng Q, Tang S (2023) Identification of Cuproptosis-Related Genes in Nonalcoholic Fatty Liver Disease. Oxid Med Cell Longev 2023:9245667. https://doi.org/10.1155/2023/9245667

Article  PubMed  PubMed Central  CAS  Google Scholar 

Wu T, Wang S, Liu Y, Bai X, Shi C (2025) Roles and mechanisms of cuproptosis for reversing cancer therapeutic resistance. Int J Pharm 685:126267. https://doi.org/10.1016/j.ijpharm.2025.126267

Article  PubMed  CAS  Google Scholar 

Xiao J, Wang Y, Yang XJ (2025) Mechanism of action of cuproptosis and prospects for anti-tumor therapy. World J Clin Cases 13:104255. https://doi.org/10.12998/wjcc.v13.i24.104255

Article  PubMed  PubMed Central  Google Scholar 

Xu S, Dong K, Gao R, Yang Y, Zhou Y, Luo C, Chen W, Liu SM (2023) Cuproptosis-related signature for clinical prognosis and immunotherapy sensitivity in hepatocellular carcinoma. J Cancer Res Clin Oncol 149:12249–12263. https://doi.org/10.1007/s00432-023-05099-x

Article  PubMed  PubMed Central  CAS  Google Scholar 

Xu M, An Y, Liu X, Li X, Huang X, Gu Q, Xue M, Xue J, Tao L, Shan H, Chen X, Zhang M (2026) The molecular mechanisms of cuproptosis and its role in central nervous system diseases. Cell Signal 138:112236. https://doi.org/10.1016/j.cellsig.2025.112236

Article  PubMed  CAS  Google Scholar 

Yang Q, Zhao Y, Zhu L, Xu X, Deng H, Tong H, Chen K (2025) Cuproptosis: Revolutionizing Cancer Treatment with Copper’s Hidden Potential. DNA Cell Biol DOI. https://doi.org/10.1177/10445498251403436

Article  Google Scholar 

Yuan Y, Cao W, Zhou H, Qian H, Wang H (2021) CLTRN, Regulated by NRF1/RAN/DLD Protein Complex, Enhances Radiation Sensitivity of Hepatocellular Carcinoma Cells Through Ferroptosis Pathway. Int J Radiat Oncol Biol Phys 110:859–871. https://doi.org/10.1016/j.ijrobp.2020.12.062

Article  PubMed 

Comments (0)

No login
gif