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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Sweeney JG,Liang J,Antonopoulos A,Giovannone N,Kang S,Mondala TS,Head SR,King SL,Tani Y,Brackett D,Dell A,Murphy GF,Haslam SM,Widlund HR,Dimitroff CJ

doi

10.1038/s41467-018-05795-0

subject

Has Abstract

pub_date

2018-08-22 00:00:00

pages

3368

issue

1

issn

2041-1723

pii

10.1038/s41467-018-05795-0

journal_volume

9

pub_type

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