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Nat Commun. 2018 Aug 22;9(1):3368. doi: 10.1038/s41467-018-05795-0.

Loss of GCNT2/I-branched glycans enhances melanoma growth and survival.

Author information

1
Department of Dermatology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
2
Harvard Medical School, Boston, MA, 02115, USA.
3
Imperial College London, Division of Molecular Biosciences, Faculty of Natural Sciences, Biochemistry Building, London, SW7 2AZ, UK.
4
The Scripps Research Institute, La Jolla, CA, 92037, USA.
5
Japanese Red Cross Kinki Block Blood Center, 7-5-17 Saito Asagi, Ibaraki-shi, Osaka, 567-0085, Japan.
6
Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
7
Department of Dermatology, Brigham and Women's Hospital, Boston, MA, 02115, USA. cdimitroff@bwh.harvard.edu.
8
Harvard Medical School, Boston, MA, 02115, USA. cdimitroff@bwh.harvard.edu.

Abstract

Cancer cells often display altered cell-surface glycans compared to their nontransformed counterparts. However, functional contributions of glycans to cancer initiation and progression remain poorly understood. Here, from expression-based analyses across cancer lineages, we found that melanomas exhibit significant transcriptional changes in glycosylation-related genes. This gene signature revealed that, compared to normal melanocytes, melanomas downregulate I-branching glycosyltransferase, GCNT2, leading to a loss of cell-surface I-branched glycans. We found that GCNT2 inversely correlated with clinical progression and that loss of GCNT2 increased melanoma xenograft growth, promoted colony formation, and enhanced cell survival. Conversely, overexpression of GCNT2 decreased melanoma xenograft growth, inhibited colony formation, and increased cell death. More focused analyses revealed reduced signaling responses of two representative glycoprotein families modified by GCNT2, insulin-like growth factor receptor and integrins. Overall, these studies reveal how subtle changes in glycan structure can regulate several malignancy-associated pathways and alter melanoma signaling, growth, and survival.

PMID:
30135430
PMCID:
PMC6105653
DOI:
10.1038/s41467-018-05795-0
[Indexed for MEDLINE]
Free PMC Article

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