Unraveling mucin domains in cancer and metastasis: when protectors become predators
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Unraveling mucin domains in cancer and metastasis: when protectors become predators Koelina Ganguly 1 & Sanchita Rauth 1 & Saravanakumar Marimuthu 1 & Sushil Kumar 1,2 & Surinder K Batra 1,2
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract A dynamic mucosal layer shields the epithelial cells lining the body cavities and is made up of high molecular weight, heavily glycosylated, multidomain proteins called mucins. Mucins, broadly grouped into transmembrane and secreted mucins, are the first responders to any mechanical or chemical insult to the epithelia and help maintain tissue homeostasis. However, their intrinsic properties to protect and repair the epithelia are exploited during oncogenic processes, where mucins are metamorphosed to aid the tumor cells in their malignant journey. Diverse domains, like the variable number tandem repeats (VNTR), sea urchin sperm protein enterokinase and agrin (SEA), adhesion-associated domain (AMOP), nidogen-like domain (NIDO), epidermal growth factor-like domain (EGF), and von Willebrand factor type D domain (vWD) on mucins, including MUC1, MUC4, MUC5AC, MUC5B, and MUC16, have been shown to facilitate cell-to-cell and cell-to-matrix interactions, and cell-autonomous signaling to promote tumorigenesis and distant dissemination of tumor cells. Several obstacles have limited the study of mucins, including technical difficulties in working with these huge glycoproteins, the dearth of scientific tools, and lack of animal models; thus, the tissue-dependent and domain-specific roles of mucins during mucosal protection, chronic inflammation, tumorigenesis, and hematological dissemination of malignant cells are still unclear. Future studies should try to integrate information on the rheological, molecular, and biological characteristics of mucins to comprehensively delineate their pathophysiological role and evaluate their suitability as targets in future diagnostic and therapeutic strategies. Keywords Mucins . Metastasis . Tumorigenesis . Mucin domains . Cancer
1 Introduction A mucosal lining covers the body cavities exposed to environmental insults, including the gastrointestinal, respiratory, and urogenital tracts. The external lining made by epithelial cells is studded with highly glycosylated proteins called mucins [1]. Broadly, gel-forming and transmembrane mucins, expressed by the goblet cells and the epithelial cells, respectively, are the structural components of the mucus layer that act as armors against pathogenic attack, chemical insult, and mechanical abrasion [2]. The synthesis, processing, and secretion of these mucins are highly coordinated and evolutionarily conserved, which attests to their indispensable role as a barrier between * Surinder K Batra [email protected] 1
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
2
Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA
the environment and the parenchyma. The mucus layers on differen
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