Agrawal Praveen, Fontanals-Cirera Barbara, Sokolova Elena, Jacob Samson, Vaiana Christopher A, Argibay Diana, Davalos Veronica, McDermott Meagan, Nayak Shruti, Darvishian Farbod, Castillo Mireia, Ueberheide Beatrix, Osman Iman, Fenyö David, Mahal Lara K, Hernando Eva
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA; Biomedical Chemistry Institute, Department of Chemistry, New York University, New York, NY 10003, USA.
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
Cancer Cell. 2017 Jun 12;31(6):804-819.e7. doi: 10.1016/j.ccell.2017.05.007.
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.
异常糖基化与黑色素瘤进展的关联主要基于对细胞系的分析。在此，我们展示了一项基于系统的研究，该研究针对患者样本中与黑色素瘤转移相关的糖组变化及相应酶类展开。核心岩藻糖基化（FUT8）上调和α-1,2岩藻糖基化（FUT1、FUT2）下调被确定为转移性黑色素瘤的特征。通过体外和体内研究，我们证明FUT8是黑色素瘤转移的驱动因素，当其沉默时，可抑制侵袭和肿瘤播散。FUT8的糖蛋白靶点在包括黏附分子L1CAM在内的细胞迁移蛋白中富集。核心岩藻糖基化影响L1CAM的裂解以及L1CAM支持黑色素瘤侵袭的能力。FUT8及其靶点代表了黑色素瘤转移中的治疗靶点。
