Abstract
The mucin (MUC) family is a group of highly glycosylated macromolecules that are abundantly expressed in mammalian epithelial cells. MUC proteins contribute to the formation of the mucus barrier and thus have protective functions against infection. Interestingly, some MUC proteins are aberrantly expressed in cancer cells and are involved in cancer development and progression, including cell growth, proliferation, the inhibition of apoptosis, chemoresistance, metabolic reprogramming, and immune evasion. With their unique biological and structural features, MUC proteins have been considered promising therapeutic targets and also biomarkers for human cancer. In this review, we discuss the biological roles of the transmembrane mucins MUC1 and MUC16 in the context of hallmarks of cancer and current efforts to develop MUC1- and MUC16-targeted therapies.
Highlights
Mucins are large and highly glycosylated proteins that provide hydration and lubrication to the epithelial luminal surface of body duct, including the gastrointestinal, respiratory, and reproductive tracts
It has been reported that MUC1 is overexpressed in a variety of cancer tissues including in pancreatic, breast, ovarian, lung, and colon carcinomas [9]
Transmembrane mucins have long been considered promising anti-cancer targets because they are abnormally overexpressed in various carcinomas of the lung [39,40,41], breast [42,43,44], pancreas [45,46,47], digestive tract [48,49,50,51], and ovary [52,53]
Summary
Mucins are large and highly glycosylated proteins that provide hydration and lubrication to the epithelial luminal surface of body duct, including the gastrointestinal, respiratory, and reproductive tracts. MUC16 ( known as carbohydrate antigen 125, CA125) is the largest transmembrane mucin and is normally expressed in the epithelium of the upper respiratory tract, ocular surface, mesothelium lining body cavities (pleural, peritoneal, and pelvic cavities), internal organs, and male and female reproductive organs [16,17,18]. Even though signaling pathways via the MUC16 cytoplasmic domain are largely unknown, a strong correlation between the serum CA125/MUC16 level and ovarian cancer prognosis suggests that. MUC16 is a potential therapeutic target for the treatment of ovarian cancer [20]. The extracellular domain of membrane-bound mucins on the surface of cancer cells can be a potential target for monoclonal antibody-based cancer therapeutics [21,22]. The purpose of this review is to summarize both intrinsic and extrinsic roles of MUC1 and MUC16 in modulating tumorigenesis and the recent advances made in exploiting the therapeutic potential of these transmembrane mucins
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