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Functional Consequences of Differential O-glycosylation of MUC1, MUC4, and MUC16 (Downstream Effects on Signaling)
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Biomolecules 2016, 6(4), 39; doi:10.3390/biom6040039

Intra- and Extra-Cellular Events Related to Altered Glycosylation of MUC1 Promote Chronic Inflammation, Tumor Progression, Invasion, and Metastasis

1
Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA
2
Fondazione Ri.Med, via Bandiera 11, Palermo 90133, Italy
*
Authors to whom correspondence should be addressed.
Academic Editor: Franz-Georg Hanisch
Received: 8 July 2016 / Revised: 29 August 2016 / Accepted: 27 September 2016 / Published: 13 October 2016
(This article belongs to the Special Issue Cancer and Glycosylation)
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Abstract

Altered glycosylation of mucin 1 (MUC1) on tumor cells compared to normal epithelial cells was previously identified as an important antigenic modification recognized by the immune system in the process of tumor immunosurveillance. This tumor form of MUC1 is considered a viable target for cancer immunotherapy. The importance of altered MUC1 glycosylation extends also to its role as a promoter of chronic inflammatory conditions that lead to malignant transformation and cancer progression. We review here what is known about the role of specific cancer-associated glycans on MUC1 in protein-protein interactions and intracellular signaling in cancer cells and in their adhesion to each other and the tumor stroma. The tumor form of MUC1 also creates a different landscape of inflammatory cells in the tumor microenvironment by controlling the recruitment of inflammatory cells, establishing specific interactions with dendritic cells (DCs) and macrophages, and facilitating tumor escape from the immune system. Through multiple types of short glycans simultaneously present in tumors, MUC1 acquires multiple oncogenic properties that control tumor development, progression, and metastasis at different steps of the process of carcinogenesis. View Full-Text
Keywords: mucin 1 (MUC1); protein-protein interaction; tumor microenvironment; inflammation mucin 1 (MUC1); protein-protein interaction; tumor microenvironment; inflammation
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Cascio, S.; Finn, O.J. Intra- and Extra-Cellular Events Related to Altered Glycosylation of MUC1 Promote Chronic Inflammation, Tumor Progression, Invasion, and Metastasis. Biomolecules 2016, 6, 39.

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