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Review
. 2023 Apr 23;13(8):2605-2615.
doi: 10.7150/thno.81760. eCollection 2023.

Roles of glycosylation at the cancer cell surface: opportunities for large scale glycoproteomics

Affiliations
Review

Roles of glycosylation at the cancer cell surface: opportunities for large scale glycoproteomics

Tomislav Čaval et al. Theranostics. .

Abstract

Cell surface glycosylation has a variety of functions, and its dysregulation in cancer contributes to impaired signaling, metastasis and the evasion of the immune responses. Recently, a number of glycosyltransferases that lead to altered glycosylation have been linked to reduced anti-tumor immune responses: B3GNT3, which is implicated in PD-L1 glycosylation in triple negative breast cancer, FUT8, through fucosylation of B7H3, and B3GNT2, which confers cancer resistance to T cell cytotoxicity. Given the increased appreciation of the relevance of protein glycosylation, there is a critical need for the development of methods that allow for an unbiased interrogation of cell surface glycosylation status. Here we provide an overview of the broad changes in glycosylation at the surface of cancer cell and describe selected examples of receptors with aberrant glycosylation leading to functional changes, with emphasis on immune checkpoint inhibitors, growth-promoting and growth-arresting receptors. Finally, we posit that the field of glycoproteomics has matured to an extent where large-scale profiling of intact glycopeptides from the cell surface is feasible and is poised for discovery of new actionable targets against cancer.

Keywords: Cancer; Glycoproteomics; Glycosylation; Immune checkpoints; Mass Spectrometry.

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Conflict of interest statement

Competing Interests: The authors are employees of InterVenn Biosciences.

Figures

Figure 1
Figure 1
Aberrant glycosylation in cancer. A) Overview of general N-glycosylation changes described in cancer. Specific examples of functional consequences of aberrant N-glycosylation are depicted for the B7 family of immune checkpoints and Endothelial Growth Factor Receptor (EGFR) are in panels B and C, respectively. Figure created with BioRender.com.
Figure 2
Figure 2
Overview of approaches for cell surface (Glyco)proteomics. (Created with BioRender.com).

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