The Role of Glycosylation in Melanoma Progression

Abstract

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.

Clinical utility of a serum glycome analysis in patients with colorectal cancer

“…Physiological role of these glycans was not fully elucidated; however, multi‐antennary glycans were produced by the enzymatic activity of α‐1,6‐mannosylglycoprotein 6‐β‐ N ‐acetylglucosaminyltransferase V (GnT‐V) and were known to modulate protein's half‐life, stability, extracellular‐binding proteins, and functional activity. Upregulation of these glycans on the adhesion molecules such as integrin family was reported to be one of the mechanisms of tumor progression and metastasis 20 . Although we did not observe any marked difference in their expression between CRC and CRA, the glycans were upregulated in advanced CRC, meaning that their elevation was a universal phenomenon associated with advanced cancers, and CRC was not exceptional.…”

“…Upregulation of these glycans on the adhesion molecules such as integrin family was reported to be one of the mechanisms of tumor progression and metastasis. 20 Although we did not observe any marked difference in their expression between CRC and CRA, the glycans were upregulated in advanced CRC, meaning that their elevation was a universal phenomenon associated with advanced cancers, and CRC was not exceptional. Regarding individual glycans, the decrease in m/z 1914 was characteristic in CRC.…”

Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression

“…Such a difference of galectin-3 binding to the MCAM in melanoma and normal endothelial cells is very interesting. Given that changes of the glycosylation of cell membrane glycoproteins very commonly occur in cancer cells including melanoma [ 41 ], the binding difference of galectin-3 with the MCAM observed in melanoma and normal endothelial cells suggests possible difference of glycosylation structures of the MCAM in cancer and physiological conditions or between melanoma and endothelial cells. The revelation by an early NMR study showing the existence of two galectin-3 binding sites on MCAM [ 42 ], one involves the S- face and one F-face of the galectin-3 sugar-binding β-sheets, is in keeping with the multimode interactions of galectin-3 with the MCAM.…”

A novel glycosyltransferase-related lncRNA signature correlates with lung adenocarcinoma prognosis

“…Glycosylation changes in tumor cells usually occur in the early tumor stages, and some tumor-related glycans have been shown to be expressed in precursors of different types of cancer, making them powerful biomarkers for early diagnosis ( 18 , 45 ). Wang et al.…”