Role of Truncated O-GalNAc Glycans in Cancer Progression and Metastasis in Endocrine Cancers

Pinto, Mario De; Parameswaran, Rajeev

doi:10.3390/cancers15133266

Cited by 4 publications

(1 citation statement)

References 114 publications

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“…For example, the aberrant expression of several types of truncated O-glycans is mainly due to differences in the expression or activity of glycosyltransferases [20,21]. The most common truncated O-glycans include T antigen (Galβ1-3GalNAcα1-O-Ser/Thr), Tn antigen (GalNAcα1-O-Ser/Thr), and STn antigen (Neu5Acα2-6GalNAcα1-O-Ser/Thr), which are mainly caused by mutations in COSMC, the molecular chaperone encoding the molecule required for the formation of active C1GALT1 (core 1β1,3-galactosyltransferase) [22,23]. These abnormal glycosyltransferases and truncated O-glycans are involved in the occur-rence and progression of cancer, and serve as important biomarkers for cancer diagnosis and treatment [24,25].…”

Section: Introductionmentioning

confidence: 99%

Mucin Glycans: A Target for Cancer Therapy

Sun,

Zhang,

et al. 2023

Molecules

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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.

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Section: Introductionmentioning

confidence: 99%

Mucin Glycans: A Target for Cancer Therapy

Sun,

Zhang,

et al. 2023

Molecules

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Substrate O‐glycosylation actively regulates extracellular proteolysis

Madzharova,

Sabino,

Kalogeropoulos

et al. 2024

Protein Science

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Extracellular proteolysis critically regulates cellular and tissue responses and is often dysregulated in human diseases. The crosstalk between proteolytic processing and other major post‐translational modifications (PTMs) is emerging as an important regulatory mechanism to modulate protease activity and maintain cellular and tissue homeostasis. Here, we focus on matrix metalloproteinase (MMP)‐mediated cleavages and N‐acetylgalactosamine (GalNAc)‐type of O‐glycosylation, two major PTMs of proteins in the extracellular space. We investigated the influence of truncated O‐glycan trees, also referred to as Tn antigen, following the inactivation of C1GALT1‐specific chaperone 1 (COSMC) on the general and MMP9‐specific proteolytic processing in MDA‐MB‐231 breast cancer cells. Quantitative assessment of the proteome and N‐terminome using terminal amine isotopic labelling of substrates (TAILS) technology revealed enhanced proteolysis by MMP9 within the extracellular proteomes of MDA‐MB‐231 cells expressing Tn antigen. In addition, we detected substantial modifications in the proteome and discovered novel ectodomain shedding events regulated by the truncation of O‐glycans. These results highlight the critical role of mature O‐glycosylation in fine‐tuning proteolytic processing and proteome homeostasis by modulating protein susceptibility to proteolytic degradation. These data suggest a complex interplay between proteolysis and O‐GalNAc glycosylation, possibly affecting cancer phenotypes.

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