Epithelial-mesenchymal transition (EMT), a biological process by which polarized 
epithelial cells convert into a mesenchymal phenotype, has been implicated to 
contribute to the molecular heterogeneity of epithelial ovarian cancer (EOC). 
Here we report that a transcription factor--Grainyhead-like 2 (GRHL2) maintains 
the epithelial phenotype. EOC tumours with lower GRHL2 levels are associated 
with the Mes/Mesenchymal molecular subtype and a poorer overall survival. 
shRNA-mediated knockdown of GRHL2 in EOC cells with an epithelial phenotype 
results in EMT changes, with increased cell migration, invasion and motility. By 
ChIP-sequencing and gene expression microarray, microRNA-200b/a is identified as 
the direct transcriptional target of GRHL2 and regulates the epithelial status 
of EOC through ZEB1 and E-cadherin. Our study demonstrates that loss of GRHL2 
increases the levels of histone mark H3K27me3 on promoters and GRHL2-binding 
sites at miR-200b/a and E-cadherin genes. These findings support GRHL2 as a 
pivotal gatekeeper of EMT in EOC via miR-200-ZEB1.