Loss of GCNT2/I-branched glycans enhances melanoma growth and survival
2018
Cancer cells often display altered cell-surface
glycanscompared to their nontransformed counterparts. However, functional contributions of
glycansto 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 signaturerevealed 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
glycanstructure can regulate several malignancy-associated pathways and alter melanoma signaling, growth, and survival.
Keywords:
-
Correction
-
Source
-
Cite
-
Save
69
References
17
Citations
NaN
KQI