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.
Highlights
Malignant melanoma is a highly aggressive tumor that accounts for about 5% of all skin cancers, but is responsible for more than 80% of skin cancer-related deaths [1]
The accumulation of genetic and epigenetic changes is thought to drive progression through these steps [4]. This model describes the natural history of a portion of melanoma, experimental, clinical and epidemiological data indicate that not all melanomas arise in such a stepwise manner, and metastatic disease can arise in patients without overt primary melanoma, suggesting that melanoma progression might be more complex and less linear [5]
We have described the crucial role of aberrant glycosylation in melanoma progression
Summary
Malignant melanoma is a highly aggressive tumor that accounts for about 5% of all skin cancers, but is responsible for more than 80% of skin cancer-related deaths [1]. It is a common belief that melanoma progression is a stepwise process in which normal melanocytes evolve to metastatic disease through a series of linear steps. Common genetic alterations associated with melanoma include mutually exclusive mutations in BRAF (50–60%), NRAS (20–25%) and NF1 (14%) [7,8]. These mutations drive hyperactivation of the mitogen-activated protein kinases (MAPK) extracellular signal-regulated kinase 1 and 2 (ERK1/2) [9], which promotes tumor cell growth. Despite the remarkable responses of BRAF mutant melanoma patients to BRAF and MEK inhibitors, primary resistance or development of acquired resistance to these targeted therapies remain a significant issue. We discuss how these events of aberrant glycosylation play a role in melanoma progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
