Melanoma‐associated glycosyltransferase GCNT2 as an emerging biomarker and therapeutic target*

Perez, Monica A.; Chakraborty, Asmi; Lau, Lee Seng; Dimitroff, Charles J.

doi:10.1111/bjd.19891

Cited by 13 publications

(2 citation statements)

References 65 publications

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“…Sweeney and colleagues demonstrated that while normal epidermal melanocytes display abundant I-branches, these structures progressively diminish in primary and metastatic melanomas. This finding is in keeping with the inverse correlation between GCNT2 and melanoma progression reported by in silico and immunohistochemical analysis, suggesting that loss of GCNT2 expression could be used as a biomarker of melanoma [88]. Furthermore, this study clearly showed that knockdown of GCNT2 significantly enhances melanoma xenograft growth and three-dimensional colony formation and survival, whereas GCNT2 overexpression has the opposite effect.…”

Section: N-and I-glycan Branchingsupporting

confidence: 89%

The Role of Glycosylation in Melanoma Progression

Vellis¹,

Pietrobono²,

Stecca³

2021

Cells

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Malignant melanoma is the most aggressive form of skin cancer, which originates from the malignant transformation of melanocytes, the melanin-producing cells of the skin. Melanoma progression is typically described as a stepwise process in which metastasis formation ensues late during disease. A large body of evidence has shown that the accumulation of genetic and epigenetic alterations drives melanoma progression through the different steps. Mortality in melanoma is associated with metastatic disease. Accordingly, early-stage melanoma can be cured in the majority of cases by surgical excision, while late-stage melanoma is a highly lethal disease. Glycosylation is a post-translational modification that involves the transfer of glycosyl moieties to specific amino acid residues of proteins to form glycosidic bonds through the activity of glycosyltransferases. Aberrant glycosylation is considered a hallmark of cancer as it occurs in the majority of tumor types, including melanoma. The most widely occurring glycosylation changes in melanoma are represented by sialylation, fucosylation, and N- and I-glycan branching. In this review, we discuss the role of glycosylation in melanoma and provide insights on the mechanisms by which aberrant glycosylation promotes melanoma progression through activation of invasion and metastasis, immune evasion and cell proliferation.

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Section: N-and I-glycan Branchingsupporting

confidence: 89%

The Role of Glycosylation in Melanoma Progression

Vellis¹,

Pietrobono²,

Stecca³

2021

Cells

View full text Add to dashboard Cite

show abstract

“…Aberrant glycosylation, indeed, plays an important role in melanoma cells, where it promotes a pro-invasive and/or pro-metastatic phenotype [ 10 , 11 ]. Several glycosyltransferases, enzymes responsible transferring specific glycans to proteins and lipids, showed abnormal abundances in metastatic cells, determining a corresponding abnormal amount of their enzymatic products [ 12 – 14 ]. Additionally, tumour hypersialylation promotes melanoma immune escape [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Total serum N-glycans associate with response to immune checkpoint inhibition therapy and survival in patients with advanced melanoma

et al. 2023

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Background Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of melanoma and other cancers. However, no reliable biomarker of survival or response has entered the clinic to identify those patients with melanoma who are most likely to benefit from ICIs. Glycosylation affects proteins and lipids’ structure and functions. Tumours are characterized by aberrant glycosylation which may contribute to their progression and hinder an effective antitumour immune response. Methods We aim at identifying novel glyco-markers of response and survival by leveraging the N-glycome of total serum proteins collected in 88 ICI-naive patients with advanced melanoma from two European countries. Samples were collected before and during ICI treatment. Results We observe that responders to ICIs present with a pre-treatment N-glycome profile significantly shifted towards higher abundancy of low-branched structures containing lower abundances of antennary fucose, and that this profile is positively associated with survival and a better predictor of response than clinical variables alone. Conclusion While changes in serum protein glycosylation have been previously implicated in a pro-metastatic melanoma behaviour, we show here that they are also associated with response to ICI, opening new avenues for the stratification of patients and the design of adjunct therapies aiming at improving immune response.

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Altered glycosylation in cancer: molecular functions and therapeutic potential

Xu,

Peng,

Jiang

et al. 2024

Cancer Communications

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Glycosylation, a key mode of protein modification in living organisms, is critical in regulating various biological functions by influencing protein folding, transportation, and localization. Changes in glycosylation patterns are a significant feature of cancer, are associated with a range of pathological activities in cancer‐related processes, and serve as critical biomarkers providing new targets for cancer diagnosis and treatment. Glycoproteins like human epidermal growth factor receptor 2 (HER2) for breast cancer, alpha‐fetoprotein (AFP) for liver cancer, carcinoembryonic antigen (CEA) for colon cancer, and prostate‐specific antigen (PSA) for prostate cancer are all tumor biomarkers approved for clinical use. Here, we introduce the diversity of glycosylation structures and newly discovered glycosylation substrate—glycosylated RNA (glycoRNA). This article focuses primarily on tumor metastasis, immune evasion, metabolic reprogramming, aberrant ferroptosis responses, and cellular senescence to illustrate the role of glycosylation in cancer. Additionally, we summarize the clinical applications of protein glycosylation in cancer diagnostics, treatment, and multidrug resistance. We envision a promising future for the clinical applications of protein glycosylation.

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Melanoma‐associated glycosyltransferase GCNT2 as an emerging biomarker and therapeutic target*

Cited by 13 publications

References 65 publications

The Role of Glycosylation in Melanoma Progression

The Role of Glycosylation in Melanoma Progression

Total serum N-glycans associate with response to immune checkpoint inhibition therapy and survival in patients with advanced melanoma

Altered glycosylation in cancer: molecular functions and therapeutic potential

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