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A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis.
Cancer Cell ( IF 50.3 ) Pub Date : 2017-06-12 , DOI: 10.1016/j.ccell.2017.05.007
Praveen Agrawal , Barbara Fontanals-Cirera , Elena Sokolova , Samson Jacob , Christopher A. Vaiana , Diana Argibay , Veronica Davalos , Meagan McDermott , Shruti Nayak , Farbod Darvishian , Mireia Castillo , Beatrix Ueberheide , Iman Osman , David Fenyö , Lara K. Mahal , Eva Hernando

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.

中文翻译:

系统生物学方法确定FUT8是黑色素瘤转移的驱动因素。

异常糖基化与黑色素瘤进展的关联主要基于细胞系的分析。在这里,我们介绍了基于糖基化变化和与患者样品中黑色素瘤转移相关的相应酶的基于系统的研究。核心岩藻糖基化(FUT8)的上调和α-1,2岩藻糖基化(FUT1,FUT2)的下调被确定为转移性黑色素瘤的特征。使用体外和体内研究,我们证明FUT8是黑色素瘤转移的驱动力,当沉默时,它抑制了侵袭和肿瘤扩散。FUT8的糖蛋白靶标富含细胞迁移蛋白,包括粘附分子L1CAM。核心岩藻糖基化影响L1CAM裂解和L1CAM支持黑色素瘤侵袭的能力。FUT8及其靶标代表黑色素瘤转移的治疗靶标。
更新日期:2017-06-13
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