GLS1 mediates SREBP-1 to promote lipid metabolism in hepatocellular carcinoma through PI3K/AKT/mTORC1 signaling pathway

Abstract

Abstract Cancer cells are characterized by altered metabolism. As the key enzyme in cancer cells that promotes glutamine catabolism to glutamate and ammonia, glutaminase 1 (GLS1) is highly associated with a variety of human malignancies. However, its role in lipid metabolism in hepatocellular carcinoma (HCC) remains to be revealed. Our findings show that GLS1 is not only significantly highly expressed in HCC, but also negatively correlates with clinical prognosis. Further studies showed that GLS1 promotes lipid accumulation and new fatty acid synthesis in HCC. In addition, GLS1 promotes lipid accumulation and cell growth by upregulating the increased 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 PI3K/AKT/mTOR activation. Taken together, our study suggests that GLS1 mediates SREBP-1 to promote lipid metabolism in HCC through the PI3K/AKT/mTORC1 signaling pathway, which may be a novel idea that GLS1 has the potential to be a biomarker for HCC as well as a target for drug therapy.