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

Nature communications | 2018

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.

Pubmed ID: 30135430 RIS Download

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA173610
  • Agency: U.S. Department of Health & Human Services | National Institutes of Health (NIH), International
    Id: F31CA171520
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI125476
  • Agency: Wellcome Trust, United Kingdom
    Id: 082098
  • Agency: American Association of Immunologists (American Association of Immunologists, Inc.), International
    Id: Immunology Fellowship
  • Agency: NCI NIH HHS, United States
    Id: F31 CA171520
  • Agency: U.S. Department of Health & Human Services | National Institutes of Health (NIH), International
    Id: R21AI125476
  • Agency: U.S. Department of Health & Human Services | National Institutes of Health (NIH), International
    Id: R01CA173610
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Biotechnology and Biological Sciences Research Council (BBSRC), International
    Id: BBF0083091

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