J Liver Cancer.  2025 Mar;25(1):1-3. 10.17998/jlc.2025.03.07.

Antitumor role of L-arginine and argininosuccinate synthetase 1 in hepatocellular carcinoma: direct and immunological mechanisms

• Eun HS

• KMID: 2567057
• DOI: http://doi.org/10.17998/jlc.2025.03.07

Figure

• 

  Figure 1. Diagram of hepatocellular carcinoma inhibition mechanisms by argininosuccinate synthetase 1 (ASS1) and L-arginine through direct and indirect pathways. NOS, nitric oxide synthase; PKM1, pyruvate kinase muscle isoform 1; PKM2, pyruvate kinase muscle isoform 2; MAPK, mitogen-activated protein kinase; PI3K, phosphatidylinositol 3-kinase; mTOR, mammalian target of rapamycin; NO, nitric oxide.

Reference

References

1. Kim JS, Choi WM, Kim HI, Chung SW, Choi J, Lee D, et al. Synergistic effects of L-arginine and argininosuccinate synthetase 1 in inducing apoptosis in hepatocellular carcinoma. J Liver Cancer. 2025; 25:79–90.

2. Kim S, Lee M, Song Y, Lee SY, Choi I, Park IS, et al. Argininosuccinate synthase 1 suppresses tumor progression through activation of PERK/eIF2α/ATF4/CHOP axis in hepatocellular carcinoma. J Exp Clin Cancer Res. 2021; 40:127.

3. Tao X, Zuo Q, Ruan H, Wang H, Jin H, Cheng Z, et al. Argininosuccinate synthase 1 suppresses cancer cell invasion by inhibiting STAT3 pathway in hepatocellular carcinoma. Acta Biochim Biophys Sin (Shanghai). 2019; 51:263–276.

4. Chen M, Zhang C, Liu W, Du X, Liu X, Xing B. Long noncoding RNA LINC01234 promotes hepatocellular carcinoma progression through orchestrating aspartate metabolic reprogramming. Mol Ther. 2022; 30:2354–2369.

5. Jeong JM, Choi SE, Shim YR, Kim HH, Lee YS, Yang K, et al. CX3 CR1 + macrophages interact with HSCs to promote HCC through CD8 + T-cell suppression. Hepatology. 2024; Jul. 19. doi: 10.1097/HEP.0000000000001021. [Epub ahead of print].

6. Geiger R, Rieckmann JC, Wolf T, Basso C, Feng Y, Fuhrer T, et al. L-arginine modulates T cell metabolism and enhances survival and anti-tumor activity. Cell. 2016; 167:829–842. e13.