Wilms’ tumor 1 (<i>WT1</i>) promotes ovarian cancer progression by regulating E-cadherin and ERK1/2 signaling

Wilms’ tumor 1 (<i>WT1</i>) is reported to play an important role in tumor invasion and metastasis, two hallmarks of ovarian cancer (OC) that influence treatment efficacy and prognosis. However, the specific roles and underlying mechanisms of <i>WT1</i> in OC have not been fully understood. Here, we investigated the potential function and signaling pathways of <i>WT1</i> in OC cells. We showed that WT1 was significantly upregulated in human OC tissues and closely associated with OC type, grade and FIGO stage. In cultured cells and xenograft mouse models, <i>WT1</i> depletion significantly inhibited cell migration and invasion, reversed epithelial–mesenchymal transition (EMT), and prevented metastasis of OC cells. We further demonstrated that <i>WT1</i> inhibited E-cadherin expression via targeting <i>E-cadherin</i> gene promoter by chromatin immunoprecipitation and luciferase reporter assay. Moreover, ERK1/2 activation was suppressed upon <i>WT1</i> silencing. Inhibiting ERK1/2 phosphorylation increased E-cadherin expression and suppressed WT1-induced OC cell migration and invasion. Taken together, our study reveals <i>WT1</i> exerts a tumor-promoting role in OC, enhancing EMT through negative modulation of E-cadherin expression via ERK1/2 signaling. <i>WT1</i> may represent a novel therapeutic target that may improve the prognosis of OC.