biostudies-literatureChen SOpen Project of Key Laboratory of Tumor Immunopathology, Ministry of EducationNatural Science Foundation of Chongqing MunicipalityKuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical UniversitySenior Medical Talents Program of Chongqing for Young, and Middle-agedNational Natural Science Foundation of ChinaYoung and Middle-aged Senior Medical Talents Studio of Chongqing2.Chongqing Natural Science Foundatione2402703https://www.ebi.ac.uk/biostudies/studies/S-EPMC11615744biostudies-literatureUnknown11(45)Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. Numerous studies have shown that metabolic reprogramming is crucial for the development of HCC. Carbamoyl phosphate synthase 1 (CPS1), a rate-limiting enzyme in urea cycle, is an abundant protein in normal hepatocytes, however, lacking systemic research in HCC. It is found that CPS1 is low-expressed in HCC tissues and circulating tumor cells, negatively correlated with HCC stage and prognosis. Further study reveals that CPS1 is a double-edged sword. On the one hand, it inhibits the activity of phosphatidylcholine-specific phospholipase C to block the biosynthesis of diacylglycerol (DAG), leading to the downregulation of the DAG/protein kinase C pathway to inhibit invasion and metastasis of cancer cells. On the other hand, CPS1 promotes cell proliferation by increasing intracellular S-adenosylmethionin to enhance the m6A modification of solute carrier family 1 member 3 mRNA, a key transporter for aspartate intake. Finally, CPS1 overexpressing adeno-associated virus can dampen HCC progression. Collectively, this results uncovered that CPS1 is a switch between HCC proliferation and metastasis by increasing intracellular aspartate level.Advanced science (Weinheim, Baden-Wurttemberg, Germany)Loss of Carbamoyl Phosphate Synthetase 1 Potentiates Hepatocellular Carcinoma Metastasis by Reducing Aspartate Level.PMC11615744CSTB2022NSCQ-MSX103882373002020jsz604CSTB2022NSCQ‐MSX1038CSTB2022NSCQ‐MSX0775CSTB2022NSCQ-MSX101082203791CSTB2022NSCQ‐MSX1010CSTB2022NSCQ-MSX077513-004-009Liu HZhou LYang MZhao WZhou YZhou ZChen ZSYang ZHe SWang QTang QHu MSong SLiao SChen SWu XfalseLoss of Carbamoyl Phosphate Synthetase 1 Potentiates Hepatocellular Carcinoma Metastasis by Reducing Aspartate Level.Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. Numerous studies have shown that metabolic reprogramming is crucial for the development of HCC. Carbamoyl phosphate synthase 1 (CPS1), a rate-limiting enzyme in urea cycle, is an abundant protein in normal hepatocytes, however, lacking systemic research in HCC. It is found that CPS1 is low-expressed in HCC tissues and circulating tumor cells, negatively correlated with HCC stage and prognosis. Further study reveals that CPS1 is a double-edged sword. On the one hand, it inhibits the activity of phosphatidylcholine-specific phospholipase C to block the biosynthesis of diacylglycerol (DAG), leading to the downregulation of the DAG/protein kinase C pathway to inhibit invasion and metastasis of cancer cells. On the other hand, CPS1 promotes cell proliferation by increasing intracellular S-adenosylmethionin to enhance the m6A modification of solute carrier family 1 member 3 mRNA, a key transporter for aspartate intake. Finally, CPS1 overexpressing adeno-associated virus can dampen HCC progression. Collectively, this results uncovered that CPS1 is a switch between HCC proliferation and metastasis by increasing intracellular aspartate level.2024-01-01T00:00:00Z2024 Dec2026-06-03T05:39:44.408Z2025-04-04T01:58:22.491ZS-EPMC116157443938745210.1002/advs.202402703