Endometrial cancer (EC) is the most common gynecologic malignancy in world. It has been reported that the mutation rate of FBXW7 is frequent in EC, but the specific functions of FBXW7 remain unknown in EC. In the present study, we revealed the role and mechanism of FBXW7 in EC cells. Compared with adjacent nontumor tissues, the FBXW7 expression level was lower in EC tissues. However, the level of STYX was in contrast with the expression of FBXW7 in EC tissues. And STYX interacted with FBXW7 and then down-regulated its expression level in EC. Over-expression of FBXW7 inhibited cell proliferation and facilitated apoptosis in EC cells, whereas silencing FBXW7 acted an opposite effect on EC cells. And the process of FBXW7 participated the proliferation and apoptosis in EC was regulated by STYX. FBXW7 suppressed the expression of Notch pathway related protein, and further inhibited the phosphorylation of mTOR. In addition, we also found that mTOR activitor (MHY1485) and Notch activator (Jagged-1) reversed the effect of over-expressing FBXW7 on cell proliferation and cell apoptosis. And Notch inhibitor (DAPT) counteracted the impact of over-expressing STYX on cell proliferation and cell apoptosis. Collectively, the present study verified that STYX inhibited the expression level of FBXW7 in EC, and then promoted cell proliferation but suppressed apoptosis through Notch-mTOR signaling pathway, which promoted carcinogenesis and progression of EC.
Keywords: FBXW7; STYX; apoptosis; endometrial cancer; proliferation.
© 2020 The Author(s).