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

Overview

Journal Adv Sci (Weinh)

Specialty Biomedical Engineering

Date 2024 Oct 10

PMID 39387452

Authors

Siyuan Chen

Qin Tang

Manqiu Hu

Sijie Song

Xiaohong Wu

You Zhou

Zihan Yang

Siqi Liao

Li Zhou

Qingliang Wang

Hongtao Liu

Mengsu Yang

Zhe-Sheng Chen

Wei Zhao

Song He

Zhihang Zhou

Affiliations

Soon will be listed here.

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.

Citing Articles

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

Chen S, Tang Q, Hu M, Song S, Wu X, Zhou Y Adv Sci (Weinh). 2024; 11(45):e2402703.

PMID: 39387452 PMC: 11615744. DOI: 10.1002/advs.202402703.

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