| Glutamic-pyruvic transaminase 2(GPT2)is a glutamic transaminase that catalyzes reversible reactions and plays an important role in glutamine metabolism and tricarboxylic acid cycle(TCA cycle).Current researches on GPT2 mainly focus on glutamine metabolism and neurodevelopmental disorders.Recently,it has been reported that over-expression of GPT2 promoted tumorigenesis and tumor development in most tumors.However,the role of GPT2 in patients’ prognosis and therapeutic resistance is unclear.Our data showed that GPT2 was up-regulated in gastric cancer tissues and cell lines.In addition,the protein level of GPT2 was negatively correlated with the survival of gastric cancer patients.We treated human gastric cancer cells with different concentrations of cisplatin,and found that the gastric cancer cells with high level of GPT2 were more resistant to cisplatin than the gastric cancer cells with low level of GPT2.Then,the relationship between GPT2 and resistance to cisplatin therapy in gastric cancer was studied in GPT2 overexpression and knockdown gastric cancer cell lines.The results showed that overexpression of GPT2 decreased the cell sensitivity to cisplatin,nevertheless knockdown of GPT2 increased the cell sensitivity to cisplatin.Meanwhile,the further study revealed that overexpression of GPT2 could activate the ERK signaling pathway,regulate the expression of SOX2 and NANOG,and enhance the ability of colony formation;while knockdown of GPT2 could inhibit the ERK signaling pathway,reduce the expression of SOX2 and NANOG,and suppress the ability of colony formation.In summary,the expression of GPT2 is related to the sensitivity of gastric cancer cell to cisplatin treatment.Overexpression of GPT2 increased the resistance of gastric cancer cells to cisplatin treatment by activating the ERK signaling pathway and up-regulating the expression of stemness relevant molecular markers SOX2 and NANOG,suggesting GPT2 is a potential target for gastric cancer therapy. |
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