Ye Yanyan, Yu Bodong, Wang Hua, Yi Fengming
Department of Ultrasound, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Front Mol Biosci. 2023 Aug 11;10:1242059. doi: 10.3389/fmolb.2023.1242059. eCollection 2023.
Hepatocellular carcinoma (HCC) is a lethal disease with limited management strategies and poor prognosis. Metabolism alternations have been frequently unveiled in HCC, including glutamine metabolic reprogramming. The components of glutamine metabolism, such as glutamine synthetase, glutamate dehydrogenase, glutaminase, metabolites, and metabolite transporters, are validated to be potential biomarkers of HCC. Increased glutamine consumption is confirmed in HCC, which fuels proliferation by elevated glutamate dehydrogenase or upstream signals. Glutamine metabolism also serves as a nitrogen source for amino acid or nucleotide anabolism. In addition, more glutamine converts to glutathione as an antioxidant in HCC to protect HCC cells from oxidative stress. Moreover, glutamine metabolic reprogramming activates the mTORC signaling pathway to support tumor cell proliferation. Glutamine metabolism targeting therapy includes glutamine deprivation, related enzyme inhibitors, and transporters inhibitors. Together, glutamine metabolic reprogramming plays a pivotal role in HCC identification, proliferation, and progression.
肝细胞癌（HCC）是一种致命疾病，治疗策略有限且预后不佳。HCC中经常出现代谢改变，包括谷氨酰胺代谢重编程。谷氨酰胺代谢的组成部分，如谷氨酰胺合成酶、谷氨酸脱氢酶、谷氨酰胺酶、代谢物和代谢物转运体，已被证实是HCC的潜在生物标志物。HCC中谷氨酰胺消耗增加，这通过升高的谷氨酸脱氢酶或上游信号促进增殖。谷氨酰胺代谢还作为氨基酸或核苷酸合成代谢的氮源。此外，在HCC中，更多的谷氨酰胺转化为谷胱甘肽作为抗氧化剂，以保护HCC细胞免受氧化应激。此外，谷氨酰胺代谢重编程激活mTORC信号通路以支持肿瘤细胞增殖。针对谷氨酰胺代谢的治疗包括谷氨酰胺剥夺、相关酶抑制剂和转运体抑制剂。总之，谷氨酰胺代谢重编程在HCC的识别、增殖和进展中起关键作用。
