STYX/FBXW7 axis participates in the development of endometrial cancer cell via Notch-mTOR signaling pathway
STYX/FBXW7 axis participates in the development of endometrial cancer cell via Notch-mTOR signaling pathway
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DOI：
10.1042/bsr20200057
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发表时间：
2020-04-17
影响因子：
4
通讯作者：
Zou, Liying
中科院分区：
文献类型：
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作者：
Liu, Liheng;Jiang, Haili;Zou, Liying
子宫内膜癌是世界上最常见的妇科恶性肿瘤。已有报道称FBXW 7在食管癌中突变率较高，但8个FBXW 7在食管癌中的具体功能尚不清楚。在本研究中，我们揭示了FBXW 7在EC细胞中的作用和机制。与癌旁组织相比，FBXW 7在EC组织中的表达水平较低。STYX和FBXW 7在食管癌组织中的表达水平存在差异。STYX与FBXW 7相互作用后下调FBXW 7在EC中的表达。FBXW 7过表达可抑制EC细胞增殖并促进细胞凋亡，而沉默FBXW 7则对EC细胞产生相反的作用。FBXW 7参与了STYX对EC增殖和凋亡的调控。FBXW 7抑制Notch通路相关蛋白的表达，进一步抑制mTOR的磷酸化。此外，我们还发现mTOR激活剂（MHY 1485）和Notch激活剂（Jagged-1）逆转了过表达FBXW 7对细胞增殖和细胞凋亡的影响。而Notch抑制剂（DAFT）则可抵消STYX过表达对细胞增殖和凋亡的影响。综上所述，本研究证实STYX通过抑制FBXW 7在EC中的表达水平，进而通过Notch-mTOR信号通路促进细胞增殖，抑制细胞凋亡，从而促进EC的发生发展。
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 8 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 (DAFT) 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.