The fucose salvage pathway inhibits invadopodia formation and extracellular matrix degradation in melanoma cells
| العنوان: | The fucose salvage pathway inhibits invadopodia formation and extracellular matrix degradation in melanoma cells |
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| المؤلفون: | Eric K. Lau, Shengyu Yang, Tyler Keeley, Shengchen Lin, Daniel K. Lester |
| المصدر: | PLoS ONE, Vol 13, Iss 6, p e0199128 (2018) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Melanomas, 0301 basic medicine, Glycosylation, Invadopodium, Cell Membranes, Cancer Treatment, lcsh:Medicine, Fucose, Metastasis, Fucosyltransferases, chemistry.chemical_compound, Animal Products, Basic Cancer Research, Medicine and Health Sciences, lcsh:Science, Melanoma, Fucosylation, Cultured Tumor Cells, Staining, Multidisciplinary, biology, Chemistry, Cell Staining, Agriculture, Recombinant Proteins, Extracellular Matrix, Neoplasm Proteins, Up-Regulation, Cell biology, Phosphotransferases (Alcohol Group Acceptor), Oncology, Podosomes, Invadopodia, Fucokinase, Melanoma Cells, Hyperexpression Techniques, Biological Cultures, Cellular Structures and Organelles, Metabolic Networks and Pathways, Research Article, Fucosyltransferase, Genetic Vectors, Research and Analysis Methods, 03 medical and health sciences, Cell Line, Tumor, Gene Expression and Vector Techniques, Humans, Neoplasm Invasiveness, Fucosidase, Molecular Biology Techniques, Molecular Biology, Molecular Biology Assays and Analysis Techniques, lcsh:R, Cancers and Neoplasms, Biology and Life Sciences, Membrane Proteins, Cell Biology, Cell Cultures, 030104 developmental biology, Specimen Preparation and Treatment, biology.protein, Gelatin, lcsh:Q, Drug Screening Assays, Antitumor, Protein Processing, Post-Translational |
| الوصف: | 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. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e414a9a38793db6e050858e3ad20b7ccTest https://doi.org/10.1371/journal.pone.0199128Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e414a9a38793db6e050858e3ad20b7cc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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