Glutamine metabolic reprogramming in hepatocellular carcinoma

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.

Automated summary

Hepatocellular carcinoma (HCC) is a lethal disease with limited management strategies and poor prognosis. Metabolism alterations, particularly glutamine metabolic reprogramming, play a pivotal role in HCC identification, proliferation, and progression. Glutamine metabolism components and their related biomarkers have been identified in HCC, including glutamine synthetase, glutamate dehydrogenase, glutaminase, metabolites, and metabolite transporters. Targeting glutamine metabolic reprogramming through deprivation, enzyme inhibitors, and transporter inhibitors has emerged as a potential approach for HCC therapy.