| Literature DB >> 28609658 |
Praveen Agrawal1, Barbara Fontanals-Cirera2, Elena Sokolova2, Samson Jacob3, Christopher A Vaiana4, Diana Argibay2, Veronica Davalos2, Meagan McDermott4, Shruti Nayak5, Farbod Darvishian2, Mireia Castillo6, Beatrix Ueberheide5, Iman Osman7, David Fenyö3, Lara K Mahal8, Eva Hernando9.
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.Entities:
Keywords: FUT8; L1CAM; core fucosylation; glycomics; glycosylation; lectin array; lectin microarray; metastasis; metastatic melanoma; primary melanoma
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Year: 2017 PMID： 28609658 PMCID： PMC5649440 DOI： 10.1016/j.ccell.2017.05.007
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743