[Glutamine metabolic reprogramming in regulating the occurrence and development of osteosarcoma].

Excessive cellular proliferation and metabolic reprogramming are important characteristics of cancer cells. Cancer cells promote excessive proliferation and growth by altering coordinated metabolic pathways. In terms of glucose metabolism, most cancer cells exhibit increased glucose uptake and lactate production even under aerobic conditions, known as the Warburg effect. Increased glucose uptake not only provides energy but also supplies essential carbon sources for the biosynthesis of nucleotides, lipids, and proteins. During this process, decreased pyruvate dehydrogenase activity leads to disruption of the tricarboxylic acid cycle (TCA), thereby increasing tumor cell dependence on other nutrients. In addition to glucose, glutamine (Gln) is also a key metabolic substrate required for cancer cell growth and proliferation. It provides both carbon and nitrogen sources to support the synthesis of ribose, non-essential amino acids, citrate, and glycerol, and compensates for the reduced oxidative phosphorylation caused by the Warburg effect. In human plasma, Gln is one of the most abundant amino acids. Normal cells synthesize Gln through glutaminase (GLS), but the Gln synthesized by tumor cells is insufficient to meet the demands of rapid proliferation, resulting in "Gln dependence". Most cancers, including osteosarcoma, show significantly increased demand for Gln. Metabolic reprogramming enables tumor cells to gain survival advantages in maintaining redox homeostasis and biosynthesis while forming unique metabolic phenotypes. Focusing on key enzymes and transporters involved in Gln metabolism in osteosarcoma and identifying potential targets may provide new ideas and directions for drug development.