Mucin Glycans: A Target for Cancer Therapy

Abstract

Mucin glycans are an important component of the mucus barrier and a vital defence against physical and chemical damage as well as pathogens. There are 20 mucins in the human body, which can be classified into secreted mucins and transmembrane mucins according to their distributions. The major difference between them is that secreted mucins do not have transmembrane structural domains, and the expression of each mucin is organ and cell-specific. Under physiological conditions, mucin glycans are involved in the composition of the mucus barrier and thus protect the body from infection and injury. However, abnormal expression of mucin glycans can lead to the occurrence of diseases, especially cancer, through various mechanisms. Therefore, targeting mucin glycans for the diagnosis and treatment of cancer has always been a promising research direction. Here, we first summarize the main types of glycosylation (O-GalNAc glycosylation and N-glycosylation) on mucins and the mechanisms by which abnormal mucin glycans occur. Next, how abnormal mucin glycans contribute to cancer development is described. Finally, we summarize MUC1-based antibodies, vaccines, radio-pharmaceuticals, and CAR-T therapies using the best characterized MUC1 as an example. In this section, we specifically elaborate on the recent new cancer therapy CAR-M, which may bring new hope to cancer patients.

CD44 in Bladder Cancer

“…Alterations in the glycosylation of proteins outside the immune system can lead to those proteins becoming pro-transforming agents. The most well documented example to date is the MUC1 protein, which normally functions, when properly glycosylated, as a coactivator of transcriptional elements related to metabolic functions [ 23 ]. MUC1 overexpression has been found in many types of cancer [ 23 ], and is certainly found in bladder cancer [ 24 ].…”

“…The most well documented example to date is the MUC1 protein, which normally functions, when properly glycosylated, as a coactivator of transcriptional elements related to metabolic functions [ 23 ]. MUC1 overexpression has been found in many types of cancer [ 23 ], and is certainly found in bladder cancer [ 24 ]. Expression analysis has revealed that MUC1 expression is significantly increased in bladder tumor tissues, as well as lymphatic metastases [ 25 ].…”

CCDC88C, an O-GalNAc glycosylation substrate of GALNT6, drives breast cancer metastasis by promoting c-JUN-mediated CEMIP transcription

“…O-linked glycosylation often occurs in the Golgi and Endoplasmic Reticulum [6]. O-glycans are generated by adding Nacetylgalactosamine (GalNAc), N-acetylglucosamine, fucose, glucose, xylose, mannose, or galactose to serine (Ser) and threonine (Thr) residues of proteins [7]. O-GalNAc glycosylation (Mucin-type Oglycosylation) is initiated by a family of 20 homologous genes encoding polypeptide GalNActransferases (ppGALNTs), and the enzymatic process is initiated in in the Golgi [6,8].…”

Ectoine Enhances Mucin Production Via Restoring IL-13/IFN-γ Balance in a Murine Dry Eye Model

“…The expression of each mucin is organ- and cell-specific. Alterations in mucin expression, glycosylation, or localization have been seen in a variety of pathological conditions, such as cancers, inflammatory bowel disease, and ocular disease (see review articles 1 – 3 ).…”

“…Collectively, these mucins contribute to regulating the host-environment interactions at mucosal surfaces through various mechanisms ranging from forming physiochemical barriers to regulating signal transduction pathways in epithelial. 1 – 4 …”