Abstract
OBJECTIVES: Cancer cells exhibit altered metabolic profiles. Glutaminase 1 (GLS1), a key enzyme in cancer cells, promoting glutamine catabolism to glutamate and ammonia, is strongly associated with various human malignancies. METHODS: GLS1 promotes lipid accumulation and cell proliferation by upregulating the expression of sterol regulatory element-binding protein 1 (SREBP-1) and SREBP cleavage-activating protein (SCAP). Mechanistically, GLS1 promotes lipid metabolism in HCC cells through the activation of the PI3K/AKT/mTORC pathway. RESULTS: GLS1's role in lipid metabolism in hepatocellular carcinoma (HCC) remains unexplored. Our findings indicate that GLS1 is not only significantly overexpressed in HCC but also negatively correlates with clinical prognosis. Further investigation revealed that GLS1 drives lipid accumulation and de novo fatty acid synthesis in HCC. CONCLUSIONS: Our study suggests that GLS1 mediates SREBP-1 to drive lipid metabolism in HCC via the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin complex 1 (PI3K/AKT/mTORC1) signaling pathway, thus we present GLS1 as a potential biomarker and therapeutic target for HCC.