@article{bb2e9a432c1e452baf5bd1e7ce443ad5,
title = "A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis",
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.",
keywords = "FUT8, L1CAM, core fucosylation, glycomics, glycosylation, lectin array, lectin microarray, metastasis, metastatic melanoma, primary melanoma",
author = "Praveen Agrawal and Barbara Fontanals-Cirera and Elena Sokolova and Samson Jacob and Vaiana, {Christopher A.} and Diana Argibay and Veronica Davalos and Meagan McDermott and Shruti Nayak and Farbod Darvishian and Mireia Castillo and Beatrix Ueberheide and Iman Osman and David Feny{\"o} and Mahal, {Lara K.} and Eva Hernando",
note = "Funding Information: We thank NYU School of Medicine Histopathology and IHC Core Laboratories for tissue processing and histology, and the NYULMC Proteomics Resource Center for mass spectrometry data. These shared resources are partially supported by the Cancer Center Support Grant, P30CA016087, at the Laura and Isaac Perlmutter Cancer Center. We thank Dr. Tin Htwe Thin (Pathology core, Icahn School of Medicine at Mount Sinai) for lectin fluorescence staining. We thank Dr. Rana S. Moubarak and Alejandro Ulloa for critical reading of the manuscript. This work was funded by the Department of Defense PRCRP Discovery Award CA110602, an NYULMC (Louise and Joshua Samuelson)-Melanoma Research Alliance established investigator award, NIH/NCI R01CA2022027-01 (E.H.), and the NIH/NCI Cancer Center Support Grant P30CA016087. P.A. has been supported by a National Cancer Center fellowship. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = jun,
day = "12",
doi = "10.1016/j.ccell.2017.05.007",
language = "English (US)",
volume = "31",
pages = "804--819.e7",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",
}
