Professor Lara Mahal and colleagues published a study in Cancer Cell called, "A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis." NYU Chemistry (Mahal Group) contributors to this project include first author postdoctoral fellow Praveen Agrawal, undergraduate student Meagan McDermott and graduate student (currently a postdoc at MIT) Chris Vaiana. For the full article, with the complete author list, click here.
In Brief: Using a systems-based approach to assess glycosylation in matched primary and metastatic melanoma samples, Agrawal et al. find increased core fucosylation mediated by FUT8 in metastatic melanoma. FUT8 facilitates invasion and tumor dissemination, in part due to reduced cleavage of core- fucosylated L1CAM.
Summary: 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 a -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.
Acknowledgements: This research was supported by the Department of Defense, the National Institutes of Health and the National Cancer Center.