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Cancer Cell. 2017 Jun 12;31(6):804-819.e7. doi: 10.1016/j.ccell.2017.05.007.

A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis.

Author information

1
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA; Biomedical Chemistry Institute, Department of Chemistry, New York University, New York, NY 10003, USA.
2
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
3
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA; Institute for Systems Genetics, New York University School of Medicine, New York, NY 10016, USA.
4
Biomedical Chemistry Institute, Department of Chemistry, New York University, New York, NY 10003, USA.
5
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
6
Department of Pathology, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY 10029, USA.
7
Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA; Department of Dermatology, New York University School of Medicine, New York, NY 10016, USA.
8
Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA; Biomedical Chemistry Institute, Department of Chemistry, New York University, New York, NY 10003, USA. Electronic address: lkmahal@nyu.edu.
9
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA. Electronic address: eva.hernando-monge@nyumc.org.

Abstract

Association of aberrant glycosylation with melanoma progression is based mainly on analyses of cell lines. Here we present a systems-based study of glycomic changes and corresponding enzymes associated with melanoma metastasis in patient samples. Upregulation of core fucosylation (FUT8) and downregulation of α-1,2 fucosylation (FUT1, FUT2) were identified as features of metastatic melanoma. Using both in vitro and in vivo studies, we demonstrate FUT8 is a driver of melanoma metastasis which, when silenced, suppresses invasion and tumor dissemination. Glycoprotein targets of FUT8 were enriched in cell migration proteins including the adhesion molecule L1CAM. Core fucosylation impacted L1CAM cleavage and the ability of L1CAM to support melanoma invasion. FUT8 and its targets represent therapeutic targets in melanoma metastasis.

KEYWORDS:

FUT8; L1CAM; core fucosylation; glycomics; glycosylation; lectin array; lectin microarray; metastasis; metastatic melanoma; primary melanoma

PMID:
28609658
PMCID:
PMC5649440
DOI:
10.1016/j.ccell.2017.05.007
[Indexed for MEDLINE]
Free PMC Article

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