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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)804-819.e7
JournalCancer Cell
Volume31
Issue number6
DOIs
StatePublished - Jun 12 2017

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Keywords

  • FUT8
  • L1CAM
  • core fucosylation
  • glycomics
  • glycosylation
  • lectin array
  • lectin microarray
  • metastasis
  • metastatic melanoma
  • primary melanoma

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Agrawal, P., Fontanals-Cirera, B., Sokolova, E., Jacob, S., Vaiana, C. A., Argibay, D., Davalos, V., McDermott, M., Nayak, S., Darvishian, F., Castillo, M., Ueberheide, B., Osman, I., Fenyö, D., Mahal, L. K., & Hernando, E. (2017). A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis. Cancer Cell, 31(6), 804-819.e7. https://doi.org/10.1016/j.ccell.2017.05.007