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

doi:10.1016/j.ccell.2017.05.007

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 journal › Article › peer-review

213 Scopus citations

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 language	English (US)
Pages (from-to)	804-819.e7
Journal	Cancer Cell
Volume	31
Issue number	6
DOIs	https://doi.org/10.1016/j.ccell.2017.05.007
State	Published - Jun 12 2017
Externally published	Yes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccell.2017.05.007

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

Agrawal, P, Fontanals-Cirera, B, Sokolova, E, Jacob, S, Vaiana, CA, Argibay, D, Davalos, V, McDermott, M, Nayak, S, Darvishian, F, Castillo, M, Ueberheide, B, Osman, I, Fenyö, D, Mahal, LK & Hernando, E 2017, 'A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis', Cancer Cell, vol. 31, no. 6, pp. 804-819.e7. https://doi.org/10.1016/j.ccell.2017.05.007

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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",

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doi = "10.1016/j.ccell.2017.05.007",

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AU - Agrawal, Praveen

AU - Fontanals-Cirera, Barbara

AU - Sokolova, Elena

AU - Jacob, Samson

AU - Vaiana, Christopher A.

AU - Argibay, Diana

AU - Davalos, Veronica

AU - McDermott, Meagan

AU - Nayak, Shruti

AU - Darvishian, Farbod

AU - Castillo, Mireia

AU - Ueberheide, Beatrix

AU - Osman, Iman

AU - Fenyö, David

AU - Mahal, Lara K.

AU - Hernando, Eva

PY - 2017/6/12

Y1 - 2017/6/12

N2 - 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.

AB - 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.

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KW - glycosylation

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KW - lectin microarray

KW - metastasis

KW - metastatic melanoma

KW - primary melanoma

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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