Transmembrane Mucins: Signaling Receptors at the Intersection of Inflammation and Cancer

Abstract

Mucosal surfaces line our body cavities and provide the interaction surface between commensal and pathogenic microbiota and the host. The barrier function of the mucosal layer is largely maintained by gel-forming mucin proteins that are secreted by goblet cells. In addition, mucosal epithelial cells express cell-bound mucins that have both barrier and signaling functions. The family of transmembrane mucins consists of diverse members that share a few characteristics. The highly glycosylated extracellular mucin domains inhibit invasion by pathogenic bacteria and can form a tight mesh structure that protects cells in harmful conditions. The intracellular tails of transmembrane mucins can be phosphorylated and connect to signaling pathways that regulate inflammation, cell-cell interactions, differentiation, and apoptosis. Transmembrane mucins play important roles in preventing infection at mucosal surfaces, but are also renowned for their contributions to the development, progression, and metastasis of adenocarcinomas. In general, transmembrane mucins seem to have evolved to monitor and repair damaged epithelia, but these functions can be highjacked by cancer cells to yield a survival advantage. This review presents an overview of the current knowledge of the functions of transmembrane mucins in inflammatory processes and carcinogenesis in order to better understand the diverse functions of these multifunctional proteins.

Effects of chlorogenic acid, epicatechin gallate, and quercetin on mucin expression and secretion in the Caco‐2/HT29‐MTX cell model

“…They seem to have evolved to monitor and repair damaged epithelia, whereas this function can be "hijacked" by cancer cells (van Putten & Strijbis, 2017). They seem to have evolved to monitor and repair damaged epithelia, whereas this function can be "hijacked" by cancer cells (van Putten & Strijbis, 2017).…”

Oral epithelial membrane‐associated mucins and transcriptional changes with Sjögren's syndrome

“…Lining the apical surface of epithelial cells are one or more members of the family of membrane‐associated mucins (MAMs) consisting of genes MUCs 1 , 3 , 4 , 12 , 13 , 15 , 16 , 17 , 20 , and 21 (Corfield, ; van Putten & Strijbis, ). MAMs are comprised of a cytoplasmic domain, a transmembrane domain, and an extracellular domain containing a highly glycosylated region characteristic of mucins: tandem repeats rich in serines and threonines, coupled to oligosaccharides via specific O‐glycosidic bonds (van Putten & Strijbis, ).…”

“…Lining the apical surface of epithelial cells are one or more members of the family of membrane‐associated mucins (MAMs) consisting of genes MUCs 1 , 3 , 4 , 12 , 13 , 15 , 16 , 17 , 20 , and 21 (Corfield, ; van Putten & Strijbis, ). MAMs are comprised of a cytoplasmic domain, a transmembrane domain, and an extracellular domain containing a highly glycosylated region characteristic of mucins: tandem repeats rich in serines and threonines, coupled to oligosaccharides via specific O‐glycosidic bonds (van Putten & Strijbis, ). The extracellular domain of MAMs is posited to aid in hydration and lubrication via hydroscopic acidic oligosaccharides (sulfated and sialylated) (Alliende et al, ), and MAMs have been shown to provide a barrier against adherence of bacteria and viruses, or to be released from the membrane to clear bound microorganisms (Menon et al, ; van Putten & Strijbis, ).…”

“…MAMs are comprised of a cytoplasmic domain, a transmembrane domain, and an extracellular domain containing a highly glycosylated region characteristic of mucins: tandem repeats rich in serines and threonines, coupled to oligosaccharides via specific O‐glycosidic bonds (van Putten & Strijbis, ). The extracellular domain of MAMs is posited to aid in hydration and lubrication via hydroscopic acidic oligosaccharides (sulfated and sialylated) (Alliende et al, ), and MAMs have been shown to provide a barrier against adherence of bacteria and viruses, or to be released from the membrane to clear bound microorganisms (Menon et al, ; van Putten & Strijbis, ). Information regarding MAMs in oral epithelia is limited, as only buccal epithelial expression of MUC1 is firmly established (Offner & Troxler, ; Ukkonen et al, ).…”

Another Brick in the Wall

“…The airways are the most common port of entry for severe infections. Here, highly specialized epithelial cells and mucins play important roles to keep us healthy [4-6]. However, bacteria can manipulate host defense, thereby creating a niche for survival in an environment that otherwise should be hostile [7-9].…”