ECB-ART-49800
Cancer Metastasis Rev
2020 Sep 01;393:647-659. doi: 10.1007/s10555-020-09896-5.
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Unraveling mucin domains in cancer and metastasis: when protectors become predators.
Ganguly K
,
Rauth S
,
Marimuthu S
,
Kumar S
,
Batra SK
.
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.
PubMed ID: 32488403
PMC ID: PMC7487023
Article link: Cancer Metastasis Rev
Grant support: [+]
R01 CA206444 NCI NIH HHS , U01 CA200466 NCI NIH HHS , R01 CA228524 NCI NIH HHS , R01 CA195586 NCI NIH HHS , U01 CA210240 NCI NIH HHS , P01 CA217798 NCI NIH HHS
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