O‑GlcNAcylation mediates endometrial cancer progression by regulating the Hippo‑YAP pathway.
O‑GlcNAcylation mediates endometrial cancer progression by regulating the Hippo‑YAP pathway.
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DOI：
10.3892/ijo.2023.5538
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发表时间：
2023-08
影响因子：
5.2
通讯作者：
Zhou F
中科院分区：
文献类型：
--
作者：
Zhai L;Yang X;Dong J;Qian L;Gao Y;Lv Y;Chen L;Chen B;Zhou F
子宫内膜癌（EC）的发病率在全球范围内迅速增加。大多数子宫内膜癌在早期被诊断出来，预后良好;然而，晚期EC患者预后不良，并出现浸润性转移。子宫内膜癌的侵袭和转移机制尚不清楚。本研究旨在探讨O-GlcNAc化对EC恶性程度的影响及其与Yes相关蛋白（雅普）的关系。结果表明，EC组织中O-GlcNAc转移酶（OGT）的表达和O-GlcNAc化水平升高，O-GlcNAc化水平降低导致EC细胞增殖、迁移和侵袭能力下降。质谱分析表明，OGT敲低减少了雅普的O-GlcNAc化。此外，发现雅普的O-GlcNAc化的减少促进其磷酸化，这反过来抑制雅普进入细胞核和下游靶基因激活，表明O-GlcNAc化水平影响EC的发展。总之，本研究结果表明，雅普是连接O-GlcNAc化和Hippo通路的关键分子，二者共同调控EC的进展。
The incidence of endometrial cancer (EC) is rapidly increasing worldwide. The majority of endometrial cancers are diagnosed at an early stage and are associated with a good prognosis; however, patients with advanced-stage EC have a poor prognosis and present with invasive metastasis. The mechanisms responsible for the invasion and metastasis of endometrial cancer remain unknown. Here, the present study aimed to examine the effects of O-GlcNAcylation on the malignancy of EC and its association with Yes-associated protein (YAP). It was found that the expression of O-GlcNAc transferase (OGT) and O-GlcNAcylation were increased in EC tissues; the decrease in O-GlcNAcylation levels was found to lead to the decreased proliferation, migration and invasion of EC cells. Mass spectrometric analysis revealed that OGT knockdown reduced the O-GlcNAcylation of YAP. Furthermore, it was found that the reduction in the O-GlcNAcylation of YAP promoted its phosphorylation, which in turn inhibited the access of YAP to the nucleus and downstream target gene activation, demonstrating that the level of O-GlcNAcylation affects the development of EC. On the whole, the findings of the present study indicate that YAP is a key molecule linking the O-GlcNAcylation and Hippo pathways, which together regulate the progression of EC.