MUC16: molecular analysis and its functional implications in benign and malignant conditions

Abstract

MUC16 is a high-molecular-weight glycoprotein that is expressed by the various epithelial cell surfaces of the human body to protect the cell layer from a myriad of insults. It is the largest mucin known to date, with an ∼22,152 aa sequence. Structurally, MUC16 is characterized into 3 distinct domains: the amino terminal, the tandem repeat, and the carboxyl terminal domain, with each domain having unique attributes. The extracellular portion of MUC16 is shed into the bloodstream and serves as a biomarker for diagnosing and monitoring patients with cancer; however, its functional role in cancer is yet to be elucidated. Several factors contribute to this challenge, which include the large protein size; the extensive glycosylation that the protein undergoes, which confers functional heterogeneity; lack of specific antibodies that detect the unique domains of MUC16; and the existence of splicing variants. Despite these limitations, MUC16 has been established as a molecule of significant application in cancer. Hence, in this review, we discuss the various aspects of MUC16, which include its discovery, structure, and biological significance both in benign and malignant conditions with an attempt to dissect its functional relevance

Transmembrane Mucin Expression and Function in Embryo Implantation and Placentation

“…The ectodomain has a massive (12,000 amino acid) O-glycosylated domain, a tandem repeat domain consisting of more than 60 repeats of 156 amino acids, and S perm-E nterokinase-A grin (SEA) domains (O'Brien et al 2001 ;Yin and Lloyd 2001 ;Gipson et al 2014 ). Indirect evidence for the occurrence of MUC16 splice variants has been suggested [discussed in Haridas et al ( 2014 )]; however, mRNA splice variants have not been rigorously identifi ed. Fragments of MUC16 released from the cell surface are the CA 125 antigens commonly used as a serum marker for certain cancers, notably ovarian and endometrial (Patsner and Yim 2013 ;Baser et al 2014 ;Felder et al 2014 ), as well as endometriosis (Spaczynski and Duleba 2003 ).…”

Oncogenic KRAS Targets MUC16/CA125 in Pancreatic Ductal Adenocarcinoma

“…MUC16 is believed to play important roles not only in normal contexts such as reproduction and proliferation, but also in pathologic states including cancer and mucosal infections. It exerts its function in cancer by many mechanisms such as migration, invasion, cell cycle control and metabolism reprogramming (16,17). Since its discovery, CA125 is usually used as a tumor marker, and many efforts have been given to its contribution to tumor malignancies, yet little is known about its regulation.…”

Human conjunctival goblet cells express the membrane associated mucin MUC16: Localization to mucin granules

“…It has a short transmembrane domain and cytoplasmic tail of 32 amino acids. (For review of MUC16 structure see Haridas et al (Haridas et al, 2014), and Govindarajan and Gipson (Govindarajan and Gipson, 2010)). An antibody, termed H185, specific to a glycan on MUC16 (Argueso et al, 2003) was found by immunoelectron microscopy to bind microplicae on the surface of human corneal and conjunctival epithelium, but the antibody was also found to bind to goblet cell mucin packets in human conjunctival epithelium obtained by impression cytology (Danjo et al, 1998).…”