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The fucose salvage pathway inhibits invadopodia formation and extracellular matrix degradation in melanoma cells

The fucose salvage pathway is a two-step process in which mammalian cells transform L-fucose into GDP-L-fucose, a universal fucose donor used by fucosyltransferases to modify glycans. Emerging evidence indicates the fucose salvage pathway and the fucosylation of proteins are altered during melanoma...

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Autores principales: Keeley, Tyler, Lin, Shengchen, Lester, Daniel K., Lau, Eric K., Yang, Shengyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010265/
https://www.ncbi.nlm.nih.gov/pubmed/29924834
http://dx.doi.org/10.1371/journal.pone.0199128
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author Keeley, Tyler
Lin, Shengchen
Lester, Daniel K.
Lau, Eric K.
Yang, Shengyu
author_facet Keeley, Tyler
Lin, Shengchen
Lester, Daniel K.
Lau, Eric K.
Yang, Shengyu
author_sort Keeley, Tyler
collection PubMed
description The fucose salvage pathway is a two-step process in which mammalian cells transform L-fucose into GDP-L-fucose, a universal fucose donor used by fucosyltransferases to modify glycans. Emerging evidence indicates the fucose salvage pathway and the fucosylation of proteins are altered during melanoma progression and metastasis. However the underlying mechanisms are not completely understood. Here, we report that the fucose salvage pathway inhibits invadopodia formation and extracellular matrix degradation by promoting α-1,2 fucosylation. Chemically or genetically increasing the fucose salvage pathway decreases invadopodium numbers and inhibits the proteolytic activity of invadopodia in WM793 melanoma cells. Inhibiting fucosylation by depleting fucokinase abrogates L-fucose-mediated inhibition of invadopodia, suggesting dependence on the fucose salvage pathway. The inhibition of invadopodium formation by L-fucose or ectopically expressed FUK could be rescued by treatment with α-1,2, but not α-1,3/α-1,4 fucosidase, implicating an α-1,2 fucose linkage-dependent anti-metastatic effect. The expression of FUT1, an α-1,2 fucosyltransferase, is remarkably down-regulated during melanoma progression, and the ectopic expression of FUT1 is sufficient to inhibit invadopodium formation and ECM degradation. Our findings indicate that the fucose salvage pathway can inhibit invadopodium formation, and consequently, invasiveness in melanoma via α-1,2 fucosylation. Re-activation of this pathway in melanoma could be useful for preventing melanoma invasion and metastasis.
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spelling pubmed-60102652018-07-06 The fucose salvage pathway inhibits invadopodia formation and extracellular matrix degradation in melanoma cells Keeley, Tyler Lin, Shengchen Lester, Daniel K. Lau, Eric K. Yang, Shengyu PLoS One Research Article The fucose salvage pathway is a two-step process in which mammalian cells transform L-fucose into GDP-L-fucose, a universal fucose donor used by fucosyltransferases to modify glycans. Emerging evidence indicates the fucose salvage pathway and the fucosylation of proteins are altered during melanoma progression and metastasis. However the underlying mechanisms are not completely understood. Here, we report that the fucose salvage pathway inhibits invadopodia formation and extracellular matrix degradation by promoting α-1,2 fucosylation. Chemically or genetically increasing the fucose salvage pathway decreases invadopodium numbers and inhibits the proteolytic activity of invadopodia in WM793 melanoma cells. Inhibiting fucosylation by depleting fucokinase abrogates L-fucose-mediated inhibition of invadopodia, suggesting dependence on the fucose salvage pathway. The inhibition of invadopodium formation by L-fucose or ectopically expressed FUK could be rescued by treatment with α-1,2, but not α-1,3/α-1,4 fucosidase, implicating an α-1,2 fucose linkage-dependent anti-metastatic effect. The expression of FUT1, an α-1,2 fucosyltransferase, is remarkably down-regulated during melanoma progression, and the ectopic expression of FUT1 is sufficient to inhibit invadopodium formation and ECM degradation. Our findings indicate that the fucose salvage pathway can inhibit invadopodium formation, and consequently, invasiveness in melanoma via α-1,2 fucosylation. Re-activation of this pathway in melanoma could be useful for preventing melanoma invasion and metastasis. Public Library of Science 2018-06-20 /pmc/articles/PMC6010265/ /pubmed/29924834 http://dx.doi.org/10.1371/journal.pone.0199128 Text en © 2018 Keeley et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Keeley, Tyler
Lin, Shengchen
Lester, Daniel K.
Lau, Eric K.
Yang, Shengyu
The fucose salvage pathway inhibits invadopodia formation and extracellular matrix degradation in melanoma cells
title The fucose salvage pathway inhibits invadopodia formation and extracellular matrix degradation in melanoma cells
title_full The fucose salvage pathway inhibits invadopodia formation and extracellular matrix degradation in melanoma cells
title_fullStr The fucose salvage pathway inhibits invadopodia formation and extracellular matrix degradation in melanoma cells
title_full_unstemmed The fucose salvage pathway inhibits invadopodia formation and extracellular matrix degradation in melanoma cells
title_short The fucose salvage pathway inhibits invadopodia formation and extracellular matrix degradation in melanoma cells
title_sort fucose salvage pathway inhibits invadopodia formation and extracellular matrix degradation in melanoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010265/
https://www.ncbi.nlm.nih.gov/pubmed/29924834
http://dx.doi.org/10.1371/journal.pone.0199128
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