gamma-Glutamyl cyclotransferase contributes to endometrial carcinoma malignant progression and upregulation of PD-L1 expression during activation of epithelial-mesenchymal transition

摘要

Recent increases in the incidence of endometrial carcinoma represent a significant risk to women's health. We found that gamma-glutamyl cyclotransferase (GGCT) was significantly up-regulated in endometrial carcinoma tissues and cells, which suggested that it may be a potential target for treatment of endometrial carcinoma. Furthermore, the impact of GGCT on proliferation, migration, and invasion of endometrial carcinoma has been demonstrated in vitro and in vivo using GGCT silencing and overexpression techniques. In addition, the epithelial-mesenchymal transition (EMT) was significantly inhibited in response to GGCT knockdown, which indicated that GGCT may contribute endometrial carcinoma malignancy during activation of the EMT. We also found that GGCT regulated PD-L1 expression during EMT activation. Furthermore, co-culture of endometrial carcinoma cells with CD8(+) T lymphocytes showed that downregulation of PD-L1 expression following GGCT knockdown contributed to the killing activity of CD8(+) T lymphocytes on endometrial carcinoma cells. In conclusion, our study showed that GGCT contributed to malignant progression and upregulation of PD-L1 expression of endometrial carcinoma, and may be a potential target for treatment of endometrial carcinoma.