Loss of Carbamoyl Phosphate Synthetase 1 Potentiates Hepatocellular Carcinoma Metastasis by Reducing Aspartate Level

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Abstract: 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.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: Loss of Carbamoyl Phosphate Synthetase 1 Potentiates Hepatocellular Carcinoma Metastasis by Reducing Aspartate Level ; day:10 ; month:10 ; year:2024 ; extent:17
Advanced science ; (10.10.2024) (gesamt 17)

Creator: Chen, Siyuan
Tang, Qin
Hu, Manqiu
Song, Sijie
Wu, Xiaohong
Zhou, You
Yang, Zihan
Liao, Siqi
Zhou, Li
Wang, Qingliang
Liu, Hongtao
Yang, Mengsu
Chen, Zhe‐Sheng
Zhao, Wei
He, Song
Zhou, Zhihang

DOI: 10.1002/advs.202402703

URN: urn:nbn:de:101:1-2410101432475.787024256591

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 15.08.2025, 7:24 AM CEST

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Chen, Siyuan
Tang, Qin
Hu, Manqiu
Song, Sijie
Wu, Xiaohong
Zhou, You
Yang, Zihan
Liao, Siqi
Zhou, Li
Wang, Qingliang
Liu, Hongtao
Yang, Mengsu
Chen, Zhe‐Sheng
Zhao, Wei
He, Song
Zhou, Zhihang

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Loss of Carbamoyl Phosphate Synthetase 1 Potentiates Hepatocellular Carcinoma Metastasis by Reducing Aspartate Level

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