Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasion
Abstract Cancer cells experience metabolic reprogramming to enhance the synthesis of nitrogen and carbon, facilitating the production of macromolecules essential for tumor proliferation and growth. A central strategy in this process involves reducing catabolic activities and managing nitrogen, there...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02328-3 |
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| author | Yiyi Shou Ruiqi Liu Hao Xiong Keke Xu Xiaoyan Chen Luanluan Huang Yitian Zhang Hailong Sheng Haibo Zhang Yanwei Lu |
| author_facet | Yiyi Shou Ruiqi Liu Hao Xiong Keke Xu Xiaoyan Chen Luanluan Huang Yitian Zhang Hailong Sheng Haibo Zhang Yanwei Lu |
| author_sort | Yiyi Shou |
| collection | DOAJ |
| description | Abstract Cancer cells experience metabolic reprogramming to enhance the synthesis of nitrogen and carbon, facilitating the production of macromolecules essential for tumor proliferation and growth. A central strategy in this process involves reducing catabolic activities and managing nitrogen, thereby improving the efficiency of nitrogen utilization. The urea cycle (UC), conventionally recognized for its role in detoxifying excess nitrogen in the liver, is pivotal in this metabolic transition. Beyond the hepatic environment, the differential expression of UC enzymes facilitates the utilization of nitrogen for the synthesis of metabolic intermediates, thereby addressing the cellular metabolic requirements, especially under conditions of nutrient scarcity. In oncogenic contexts, the expression and regulation of UC enzymes undergo substantial modification, promoting metabolic reprogramming to optimize nitrogen assimilation into cellular biomass. This reconfigured UC not only enhances tumor cell survival but also plays a pivotal role in the reorganization of the tumor microenvironment (TME), thereby aiding in immune evasion. This review examines the mechanistic underpinnings of urea cycle dysregulation (UCD) in cancer, highlighting its dynamic roles across various tumor types and stages, as well as the therapeutic implications of these alterations. Understanding how UC relaxation promotes metabolic flexibility and immune evasion may help develop novel therapeutic strategies that target tumor metabolism and enhance anti-cancer immunity. |
| format | Article |
| id | doaj-art-85683a8439f84d4db6126e3f1ea8d101 |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-85683a8439f84d4db6126e3f1ea8d1012025-08-20T04:01:35ZengBMCCell Communication and Signaling1478-811X2025-07-0123111510.1186/s12964-025-02328-3Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasionYiyi Shou0Ruiqi Liu1Hao Xiong2Keke Xu3Xiaoyan Chen4Luanluan Huang5Yitian Zhang6Hailong Sheng7Haibo Zhang8Yanwei Lu9School of Clinical Medicine, Hangzhou Normal UniversityDepartment of Pathology, Tongde Hospital of Zhejiang ProvinceCancer Center, Department of Radiation Oncology, Zhejiang Provincial People’s Hospital(Affiliated People’s Hospital), Hangzhou Medical CollegeCancer Center, Department of Radiation Oncology, Zhejiang Provincial People’s Hospital(Affiliated People’s Hospital), Hangzhou Medical CollegeCancer Center, Department of Radiation Oncology, Zhejiang Provincial People’s Hospital(Affiliated People’s Hospital), Hangzhou Medical CollegeCancer Center, Department of Radiation Oncology, Zhejiang Provincial People’s Hospital(Affiliated People’s Hospital), Hangzhou Medical CollegePeople’s Hospital of Jinxiang CountyCancer Center, Department of Radiation Oncology, Zhejiang Provincial People’s Hospital(Affiliated People’s Hospital), Hangzhou Medical CollegeCancer Center, Department of Radiation Oncology, Zhejiang Provincial People’s Hospital(Affiliated People’s Hospital), Hangzhou Medical CollegeCancer Center, Department of Radiation Oncology, Zhejiang Provincial People’s Hospital(Affiliated People’s Hospital), Hangzhou Medical CollegeAbstract Cancer cells experience metabolic reprogramming to enhance the synthesis of nitrogen and carbon, facilitating the production of macromolecules essential for tumor proliferation and growth. A central strategy in this process involves reducing catabolic activities and managing nitrogen, thereby improving the efficiency of nitrogen utilization. The urea cycle (UC), conventionally recognized for its role in detoxifying excess nitrogen in the liver, is pivotal in this metabolic transition. Beyond the hepatic environment, the differential expression of UC enzymes facilitates the utilization of nitrogen for the synthesis of metabolic intermediates, thereby addressing the cellular metabolic requirements, especially under conditions of nutrient scarcity. In oncogenic contexts, the expression and regulation of UC enzymes undergo substantial modification, promoting metabolic reprogramming to optimize nitrogen assimilation into cellular biomass. This reconfigured UC not only enhances tumor cell survival but also plays a pivotal role in the reorganization of the tumor microenvironment (TME), thereby aiding in immune evasion. This review examines the mechanistic underpinnings of urea cycle dysregulation (UCD) in cancer, highlighting its dynamic roles across various tumor types and stages, as well as the therapeutic implications of these alterations. Understanding how UC relaxation promotes metabolic flexibility and immune evasion may help develop novel therapeutic strategies that target tumor metabolism and enhance anti-cancer immunity.https://doi.org/10.1186/s12964-025-02328-3Urea cycleCancer metabolismMetabolic reprogrammingTumor immunogenicityCancer treatment |
| spellingShingle | Yiyi Shou Ruiqi Liu Hao Xiong Keke Xu Xiaoyan Chen Luanluan Huang Yitian Zhang Hailong Sheng Haibo Zhang Yanwei Lu Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasion Cell Communication and Signaling Urea cycle Cancer metabolism Metabolic reprogramming Tumor immunogenicity Cancer treatment |
| title | Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasion |
| title_full | Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasion |
| title_fullStr | Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasion |
| title_full_unstemmed | Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasion |
| title_short | Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasion |
| title_sort | urea cycle dysregulation a new frontier in cancer metabolism and immune evasion |
| topic | Urea cycle Cancer metabolism Metabolic reprogramming Tumor immunogenicity Cancer treatment |
| url | https://doi.org/10.1186/s12964-025-02328-3 |
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