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Unraveling mucin domains in cancer and metastasis: when protectors become predators

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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.

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Acknowledgments

We thank Dr. Jessica Mercer for editorial contribution to the manuscript.

Funding

This authors’ work was partly supported by funding from the National Institutes of Health (P01CA217798, U01 CA210240, U01 CA200466, R01 CA206444, R01 CA228524, and R01 CA195586).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA

    Koelina Ganguly, Sanchita Rauth, Saravanakumar Marimuthu, Sushil Kumar & Surinder K Batra

  2. Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA

    Sushil Kumar & Surinder K Batra

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  1. Koelina Ganguly
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  2. Sanchita Rauth
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Correspondence to Surinder K Batra.

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SKB is one of the co-founders of the Sanguine Diagnostic and Therapeutics, Inc.

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Ganguly, K., Rauth, S., Marimuthu, S. et al. Unraveling mucin domains in cancer and metastasis: when protectors become predators. Cancer Metastasis Rev 39, 647–659 (2020). https://doi.org/10.1007/s10555-020-09896-5

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