The Epithelial-Mesenchymal Transition and the Estrogen-Signaling in Ovarian Cancer
Epithelial ovarian cancer is the leading cause of death for gynecological cancer in most of the Western world; lethality ensues from the occurrence of occult metastasis within the peritoneal cavity, a process requiring the acquisition of capacity for migration and invasiveness by ovarian tumor cells (metastatic phenotype), and characterized by a complex series of interrelated cellular events. Unlike most carcinomas that dedifferentiate during neoplastic progression with loss of epithelial E-cadherin (epithelial to mesenchymal transition, EMT), ovarian carcinomas undergo transition to a more epithelial phenotype, early in tumor progression, with increased E-cadherin expression. Subsequent reacquisition of mesenchymal features is observed in late-stage tumors, and loss of E-cadherin expression or function is a factor in ovarian cancer progression. Changes in E-cadherin expression are indicative of the phenotypic plasticity that occurs in ovarian cancer, with a variety of signal transduction pathways impinging on the regulation of E-cadherin levels or subcellular distribution. Among them, the Snail transcription family, consisting of members SNAIL and SLUG, is thought to be mainly involved in the repression of E-cadherin expression, leading to EMT. E-cadherin, SNAIL, and SLUG also represent crucial targets of estrogen signaling. In this review, we discuss recent advances in the understanding of the role of estrogen signaling in the complex network underlying the phenotypic plasticity in ovarian cancer. Insight into the mechanisms involved will allow rational drug designs, aimed at the molecules critical to cellular signaling.
No Supplementary Data
Document Type: Research Article
Publication date: 2010-04-01
More about this publication?
- Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.