A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis

被引：243

作者：

Agrawal, Praveen ^{[1
,2
,3
]}

Fontanals-Cirera, Barbara ^{[1
,2
]}

Sokolova, Elena ^{[1
,2
]}

Jacob, Samson ^{[4
,5
]}

Vaiana, Christopher A. ^{[3
]}

Argibay, Diana ^{[1
,2
]}

Davalos, Veronica ^{[1
,2
]}

McDermott, Meagan ^{[3
]}

Nayak, Shruti ^{[4
]}

Darvishian, Farbod ^{[1
,2
]}

Castillo, Mireia ^{[7
]}

Ueberheide, Beatrix ^{[4
]}

Osman, Iman ^{[2
,6
]}

Fenyo, David ^{[4
,5
]}

Mahal, Lara K. ^{[2
,3
]}

Hernando, Eva ^{[1
,2
]}

机构：

[1] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA

[2] NYU, Sch Med, Perlmutter Canc Ctr, Interdisciplinary Melanoma Cooperat Grp, New York, NY 10016 USA

[3] NYU, Dept Chem, Inst Biomed Chem, New York, NY 10003 USA

[4] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA

[5] NYU, Sch Med, Inst Syst Genet, New York, NY 10016 USA

[6] NYU, Sch Med, Dept Dermatol, New York, NY 10016 USA

[7] Mt Sinai Hlth Syst, Icahn Sch Med Mt Sinai, Dept Pathol, New York, NY 10029 USA

来源：

CANCER CELL | 2017年 / 31卷 / 06期

关键词：

PROTEIN GLYCOSYLATION; HEPATOCELLULAR-CARCINOMA; TUMOR PROGRESSION; GLYCOMIC ANALYSIS; PROMOTER ANALYSIS; CELLS; CANCER; ACTIVATION; ADHESION; MODEL;

D O I：

10.1016/j.ccell.2017.05.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 alpha-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.

引用

页码：804 / +

页数：23

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