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.
Highlights
Mucin 1 (MUC1) is a heterodimeric type I transmembrane glycoprotein expressed on the apical surface of most epithelia, including mammary gland, lung, pancreas, kidney, female reproductive tract, and stomach
We recently demonstrated that cbl-interacting protein of 85 kDa (CIN85) is a MUC1-interacting protein implicated in migratory and metastatic activities of cancer cells
Overexpression and aberrant glycosylation of MUC1 on tumor cells influences many critical steps in tumor initiation, progression, and metastasis as well as in tumor immunosurveillance. We found that this hypoglycosylated tumor form of MUC1 is overexpressed during chronic inflammation and in premalignant lesions that progress to tumors
Summary
Mucin 1 (MUC1) is a heterodimeric type I transmembrane glycoprotein expressed on the apical surface of most epithelia, including mammary gland, lung, pancreas, kidney, female reproductive tract, and stomach. The MUC1-N contains the variable number of tandem repeats (VNTR) region and the SEA (sea urchin sperm protein enterokinase and agrin) domain. MUC1-CT is shown to modulate activity of the nuclear factor kappa B (NF-κB) pathway in breast cancer cells by interacting with and activating IkB kinase (IKK) family members and NF-κB p65 [15,16,17]. These new interactions of MUC1 with various proteins increase its internalization and enable nuclear localization, leading to altered signaling in cancer cells
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