The Role of MUC16 Mucin (CA125) in the Pathogenesis of Ovarian Cancer

The majority of epithelial ovarian carcinomas (EOCs) are derived from the ovarian surface epithelium (OSE). EOCs are the most lethal of all gynecological malignancies. Most patients present with advanced diseases in which tumor cells are disseminated throughout the peritoneal cavity. MUC16 serum level is a well-established marker for ovarian cancer (OC) progression and disease response to treatment. MUC16 is a high molecular weight, membrane associated-mucin, which is aberrantly expressed in advanced serous EOC. MUC16 is also expressed at the surface of corneal and respiratory epithelial cells, and the surface of female reproductive tract epithelium. It is however not expressed by the normal OSE. Like other membrane-bounded mucins, this glycosylated protein is primarily involved in the lubrification of epithelial luminal surfaces. MUC16 glycoprotein possesses unique structural motifs as compared with other membrane-bounded mucins. Its ectodomain is composed of a large heavily O-glycosylated N-terminus and a tandem repeat region with over 60 tandem repeats. MUC16 C-terminal domain (CTD) is composed of an extracellular unique region which contains a potential proteolytic cleavage site, a transmembrane domain and a short cytoplasmic tail with possible phosphorylation sites. MUC16 domains most likely have various functions resulting in activation of signalling pathways which regulate different tumor cell phenotypes. Indeed, recent functional studies have begun to uncover the unique role of MUC16 in the pathogenesis of OC. The present review will discuss the unique structure and functional roles of MUC16 in OC.