Cuproplasia and cuproptosis in hepatocellular carcinoma: mechanisms, relationship and potential role in tumor microenvironment and treatment
Abstract Background Hepatocellular carcinoma (HCC) is the main phenotype of liver cancer with a poor prognosis. Copper is vital in liver function, and HCC cells rely on it for growth and metastasis, leading to cuproplasia. Excessive copper can induce cell death, termed cuproptosis. Tumor microenviro...
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| Format: | Article |
| Language: | English |
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BMC
2025-04-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03683-4 |
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| author | Ruoyu Zhang Yunfei Tan Ke Xu Ning Huang Jian Wang Mei Liu Liming Wang |
| author_facet | Ruoyu Zhang Yunfei Tan Ke Xu Ning Huang Jian Wang Mei Liu Liming Wang |
| author_sort | Ruoyu Zhang |
| collection | DOAJ |
| description | Abstract Background Hepatocellular carcinoma (HCC) is the main phenotype of liver cancer with a poor prognosis. Copper is vital in liver function, and HCC cells rely on it for growth and metastasis, leading to cuproplasia. Excessive copper can induce cell death, termed cuproptosis. Tumor microenvironment (TME) is pivotal in HCC, especially in immunotherapy, and copper is closely related to the TME pathogenesis. However, how these two mechanisms contribute to the TME is intriguing. Main body We conducted the latest progress literature on cuproplasia and cuproptosis in HCC, and summarized their specific roles in TME and treatment strategies. The mechanisms of cuproplasia and cuproptosis and their relationship and role in TME have been deeply summarized. Cuproplasia fosters TME formation, angiogenesis, and metastasis, whereas cuproptosis may alleviate mitochondrial dysfunction and hypoxic conditions in the TME. Inhibiting cuproplasia and enhancing cuproptosis in HCC are essential for achieving therapeutic efficacy in HCC. Conclusion An in-depth analysis of cuproplasia and cuproptosis mechanisms within the TME of HCC unveils their opposing nature and their impact on copper regulation. Grasping the equilibrium between these two factors is crucial for a deeper understanding of HCC mechanisms to shed light on novel directions in treating HCC. |
| format | Article |
| id | doaj-art-ff0f047f41da4e50938cbf9ed3cc1691 |
| institution | OA Journals |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-ff0f047f41da4e50938cbf9ed3cc16912025-08-20T02:28:07ZengBMCCancer Cell International1475-28672025-04-0125112010.1186/s12935-025-03683-4Cuproplasia and cuproptosis in hepatocellular carcinoma: mechanisms, relationship and potential role in tumor microenvironment and treatmentRuoyu Zhang0Yunfei Tan1Ke Xu2Ning Huang3Jian Wang4Mei Liu5Liming Wang6Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Unit III, Gastrointestinal Cancer Center, Peking University Cancer Hospital & InstituteDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Human Anatomy, School of Basic Medical Sciences, Zhengzhou UniversityLaboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Background Hepatocellular carcinoma (HCC) is the main phenotype of liver cancer with a poor prognosis. Copper is vital in liver function, and HCC cells rely on it for growth and metastasis, leading to cuproplasia. Excessive copper can induce cell death, termed cuproptosis. Tumor microenvironment (TME) is pivotal in HCC, especially in immunotherapy, and copper is closely related to the TME pathogenesis. However, how these two mechanisms contribute to the TME is intriguing. Main body We conducted the latest progress literature on cuproplasia and cuproptosis in HCC, and summarized their specific roles in TME and treatment strategies. The mechanisms of cuproplasia and cuproptosis and their relationship and role in TME have been deeply summarized. Cuproplasia fosters TME formation, angiogenesis, and metastasis, whereas cuproptosis may alleviate mitochondrial dysfunction and hypoxic conditions in the TME. Inhibiting cuproplasia and enhancing cuproptosis in HCC are essential for achieving therapeutic efficacy in HCC. Conclusion An in-depth analysis of cuproplasia and cuproptosis mechanisms within the TME of HCC unveils their opposing nature and their impact on copper regulation. Grasping the equilibrium between these two factors is crucial for a deeper understanding of HCC mechanisms to shed light on novel directions in treating HCC.https://doi.org/10.1186/s12935-025-03683-4CopperCuproplasiaCuproptosisHepatocellular carcinomaMechanismTumor microenvironment |
| spellingShingle | Ruoyu Zhang Yunfei Tan Ke Xu Ning Huang Jian Wang Mei Liu Liming Wang Cuproplasia and cuproptosis in hepatocellular carcinoma: mechanisms, relationship and potential role in tumor microenvironment and treatment Cancer Cell International Copper Cuproplasia Cuproptosis Hepatocellular carcinoma Mechanism Tumor microenvironment |
| title | Cuproplasia and cuproptosis in hepatocellular carcinoma: mechanisms, relationship and potential role in tumor microenvironment and treatment |
| title_full | Cuproplasia and cuproptosis in hepatocellular carcinoma: mechanisms, relationship and potential role in tumor microenvironment and treatment |
| title_fullStr | Cuproplasia and cuproptosis in hepatocellular carcinoma: mechanisms, relationship and potential role in tumor microenvironment and treatment |
| title_full_unstemmed | Cuproplasia and cuproptosis in hepatocellular carcinoma: mechanisms, relationship and potential role in tumor microenvironment and treatment |
| title_short | Cuproplasia and cuproptosis in hepatocellular carcinoma: mechanisms, relationship and potential role in tumor microenvironment and treatment |
| title_sort | cuproplasia and cuproptosis in hepatocellular carcinoma mechanisms relationship and potential role in tumor microenvironment and treatment |
| topic | Copper Cuproplasia Cuproptosis Hepatocellular carcinoma Mechanism Tumor microenvironment |
| url | https://doi.org/10.1186/s12935-025-03683-4 |
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