O-GlcNAcylation mediates endometrial cancer progression by regulating the Hippo-YAP pathway

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.