Regulation and Targeting of MUCINS in Pancreatic Cancer
Surinder K. Batra, Moorthy P. Ponnusamy in Gene Regulation and Therapeutics for Cancer, 2021
Mucins are family of high molecular weight glycoproteins that have been reported to play a structural and functional role in PC pathogenesis. Both secretory mucins e.g. MUC2, MUC5AC, MUC5B, MUC6–9, and MUC19 and membrane-bound mucins e.g. MUC1, MUC3A/B, MUC4, MUC11–13, MUC15–17, and MUC20–22 have clinical significance as predictive biomarkers for disease progression and as putative therapeutic targets [14, 19]. Importantly, MUC1, MUC4, MUC5AC, and MUC16 have been thoroughly investigated for their role in PC progression [14, 20]. However, more efforts need to be directed towards the optimization of mucin-based therapeutic approaches in PC. Strategically, mucin-based diagnostic and therapeutic approaches can be divided based on their secretory and membrane-bound nature. For instance, the membrane-bound mucins like MUC1, MUC4, and MUC16 are more suitable for targeted therapies including small molecule inhibitors, antibody-based therapy, and other vaccine-based immunotherapy. In contrast, the secretory mucins MUC2 and MUC5AC are more likely to have potential as biomarkers. This chapter will highlight the significant findings related to transmembrane mucins such as MUC1, MUC 4 and MUC16 due to their well-characterized structure and biological functions. Further, the mucin-based targeting approach will emphasize the global perspective to delineate the therapeutic potentials of different membrane bound mucins in PC.
Molecular diagnosis of endometrial receptivity
Carlos Simón, Linda C. Giudice in The Endometrial Factor, 2017
The mucin family transmembrane protein lines the apical surfaces of many tissues, including endometrial epithelium. In mammals, mucins typically function in lubrication and protection. These glycoproteins provide the endometrium with a physical barrier to implantation to prevent embryo attachment; this barrier must be overcome to allow reproduction. The endometrial epithelium contains three mucins: MUC1, MUC4, and MUC16. MUC1 is the most widely studied; however, it acts differently on endometrial epithelium cells in mice and humans. During the receptive period in mice, MUC1 expression is downregulated, suggesting that it hinders attachment. In contrast, fertile women exhibit a progesterone-mediated increase in MUC1 levels during the WOI (49,50), which does not appear to occur in women with RIF (51). Specifically, the blastocyst induces a local clearance of MUC1 during adhesion to enable its implantation at that site (52). Further studies are needed to understand the observed downregulation of MUC1 during implantation, but several molecules, including disintegrin, matrix metalloproteinase (MMP)-17, and MMP-14, have been implicated in this event (53,54).
Neurogenic tumors
Eckart Haneke in Histopathology of the NailOnychopathology, 2017
Traumatic neuromas are not true tumors, but usually a reparative process. They consist of an increased and disorganized number of myelinated nerve fascicles of different sizes and shapes running in various directions. Mucin may be found in the nerves (Figure 12.1). They are embedded in a fibrotic stroma, which may sometimes even be myxoid,7 but this is not a consistent feature. A true capsule does not exist. The distal end of the regenerating nerve may infiltrate the fibrous tissue. The cells are slender spindle cells and constitute of Schwann cells, perineurial cells, and endoneural fibroblasts. Silver impregnation exhibits the axons showing a 1:1 ratio of axons and Schwann cells. Neural markers such as protein S100 and neurofilament are strongly positive: neurofilament stain highlights the axons, the myelin is positive for myelin basic protein and CD57 (Leu-7), whereas S100 as well as collagen IV stain the Schwann cells. Neurofilament stain may appear as a fine dot when the axon is cut perpendicularly or as a slender long thread-like structure when cut longitudinally. Epithelial membrane antigen is positive in the perineurial cells around the nerve bundles.
MUC16 mutations improve patients’ prognosis by enhancing the infiltration and antitumor immunity of cytotoxic T lymphocytes in the endometrial cancer microenvironment
Published in OncoImmunology, 2018
Jing Hu, Jing Sun
Mucins are high molecular weight glycoproteins that are divided into two subfamilies, secreted and transmembrane mucins.3 Mucins normally express on various types of epithelial cells and play numerous physiological roles ranging from protection against pathogenic infections to regulation of cellular signaling and transcription.4 Many studies also demonstrated that mucins were overexpressed and aberrantly glycosylated in diverse epithelial cancers to promote cancer cell growth and invasion.5–8 MUC16 is the largest transmembrane mucin and its secreted counterpart is CA125, the well-known diagnostic and adverse prognostic serum marker of gynecological malignancy.9,10 However, its roles in carcinogenesis and progression of endometrial carcinoma are not fully clear.
Prebiotic oligofructose protects against high-fat diet-induced obesity by changing the gut microbiota, intestinal mucus production, glycosylation and secretion
Published in Gut Microbes, 2022
Paola Paone, Francesco Suriano, Ching Jian, Katri Korpela, Nathalie M. Delzenne, Matthias Van Hul, Anne Salonen, Patrice D. Cani
It has been observed that during obesity and metabolic disorders the gut microbiota composition is different and this is associated with gut barrier dysfunction.3,4 Among the components of the gut barrier, the mucus layer is critical and hence has raised more attention in recent years. The mucus layer is the first line of protection of the gastrointestinal tract and the interface of communication between the gut microbiota and the host.5 It is produced and secreted by the goblet cells and mainly composed of specific proteins called mucins. Mucins are heavily glycosylated proteins with different glycans, often representing more than 80% of the mucin mass.5 The enzymes responsible for the mucin glycosylation are called glycosyltransferases and are specific for each glycan residue and for precise positions. The mucins are classified as secreted and transmembrane and the most important component of the mucus layer is the secreted mucin 2 (Muc2).
Identification of novel adhesive proteins in pearl oyster by proteomic and bioinformatic analysis
Published in Biofouling, 2021
Chuang Liu, Rongqing Zhang
Mucins (IPR023217) are a family of high molecular weight, heavily-glycosylated proteins produced by epithelial tissues in most organisms. The key characteristic of mucins is their ability to form gels. In addition, mucins can serve a variety of functions ranging from lubrication to cell signaling (Hollingsworth and Swanson 2004). Three mucin-like proteins were found in the adhesive plaques (Table 1 and Figure S5). Interestingly, mucin-like proteins were found in sea star adhesive footprints and could be involved in the formation of structural networks through oligomerization and/or crosslinking with other adhesive proteins (Hennebert et al. 2015). Although adhesives were thoroughly cleaned with water before analysis, mucin-like proteins might be contaminants from the mucus of the foot, which need to be tested by immunohistochemistry experiments in the future.
Related Knowledge Centers
- Animal
- Biomineralization
- Calcification
- Epithelium
- Glycosylation
- Nacre
- Cell Membrane
- Glycoconjugate
- Gel
- Mucin Short Variant S1