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Melanoma-associated glycosyltransferase GCNT2 as an emerging biomarker and therapeutic target.

ABSTRACT: In metastatic melanoma, with a dismal survival rate and propensity for treatment resistance and recurrence, it is critical to establish biomarkers that better predict treatment response and disease severity. The melanoma glycome, composed of complex carbohydrates termed glycans, is an under-investigated area of research, although it is gaining momentum in the cancer biomarker and therapeutics field. Novel findings suggest that glycans play a major role in influencing melanoma progression and could be exploited for prognosticating metastatic activity and/or as therapeutic targets. In this review, we discuss the role of aberrant glycosylation, particularly the specialized function of β1,6 N-acetylglucosaminyltransferase 2 (GCNT2), in melanoma pathogenesis and summarize mechanisms of GCNT2 regulation to illuminate its potential as a predictive marker and therapeutic target.

SUBMITTER: Perez M

PROVIDER: S-EPMC8373636 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Melanoma-associated glycosyltransferase GCNT2 as an emerging biomarker and therapeutic target.

Perez M M Chakraborty A A Lau L S LS Mohammed N B B NBB Dimitroff C J CJ

The British journal of dermatology 20210504 2

In metastatic melanoma, with a dismal survival rate and propensity for treatment resistance and recurrence, it is critical to establish biomarkers that better predict treatment response and disease severity. The melanoma glycome, composed of complex carbohydrates termed glycans, is an under-investigated area of research, although it is gaining momentum in the cancer biomarker and therapeutics field. Novel findings suggest that glycans play a major role in influencing melanoma progression and cou ...[more]

PMID: 33660254

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Project description:UnlabelledThe reception and integration of the plethora of signals a cell receives from its microenvironment determines the cell's fate. CD44 functions as a receptor for hyaluronan and many other extracellular matrix components, as well as a cofactor for growth factors and cytokines, and thus, CD44 is a signaling platform that integrates cellular microenvironmental cues with growth factor and cytokine signals and transduces signals to membrane-associated cytoskeletal proteins or to the nucleus to regulate a variety of gene expression levels related to cell-matrix adhesion, cell migration, proliferation, differentiation, and survival. Accumulating evidence indicates that CD44, especially CD44v isoforms, are cancer stem cell (CSC) markers and critical players in regulating the properties of CSCs, including self-renewal, tumor initiation, metastasis, and chemoradioresistance. Furthermore, there is ample evidence that CD44, especially CD44v isoforms, are valuable prognostic markers in various types of tumors. Therefore, therapies that target CD44 may destroy the CSC population, and this holds great promise for the cure of life-threatening cancers. However, many challenges remain to determining how best to use CD44 as a biomarker and therapeutic target. Here we summarize the current findings concerning the critical role of CD44/CD44v in the regulation of cancer stemness and the research status of CD44/CD44v as biomarkers and therapeutic targets in cancer. We also discuss the current challenges and future directions that may lead to the best use of CD44/CD44v for clinical applications.SignificanceMounting evidence indicates that cancer stem cells (CSCs) are mainly responsible for cancer aggressiveness, drug resistance, and tumor relapse. CD44, especially CD44v isoforms, have been identified as CSC surface markers for isolating and enriching CSCs in different types of cancers. The current findings concerning the critical role of CD44/CD44v in regulation of cancer stemness and the research status of CD44/CD44v as biomarkers and therapeutic targets in cancer are summarized. The current challenges and future directions that may lead to best use of CD44/CD44v for clinical applications are also discussed.

Dataset Information

Melanoma-associated glycosyltransferase GCNT2 as an emerging biomarker and therapeutic target.

Publications

Melanoma-associated glycosyltransferase GCNT2 as an emerging biomarker and therapeutic target.

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