Regulation of epithelial-mesenchymal transition in endometrial cancer: connecting PI3K, estrogen signaling, and microRNAs.

Endometrial cancer (EC) prognosis is dependent on many factors such as time of diagnosis, histological type, and degree of invasion. Type I EC has a more favorable prognosis as it is less prone to myometrial invasion, which is believed to be the first step in the metastatic cascade. Type II EC displays a more aggressive and motile phenotype, and therefore has a poorer prognosis. Recent work suggests that despite the epithelial nature of Type I and Type II endometrial tumors, both are capable of undergoing an epithelial-mesenchymal transition (EMT), which may facilitate myometrial invasion and metastasis. Activation of the PI3K/Akt pathway has been shown to contribute to EMT through the upregulation of EMT-associated factors. Recent research has also linked estrogen signaling and microRNAs to the regulatory mechanisms that drive EMT in EC. Understanding the intricate relationships between these pathways will provide a better understanding of metastatic progression in EC.