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Inhibition of Fucosylation in Human Invasive Ductal Carcinoma Reduces E-Selectin Ligand Expression, Cell Proliferation, and ERK1/2 and p38 MAPK Activation

2018Journal article Open access
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dc.contributor.authorCarrascal, M
dc.contributor.authorSilva, M
dc.contributor.authorRamalho, J
dc.contributor.authorPen, C
dc.contributor.authorMartins, M
dc.contributor.authorPascoal, C
dc.contributor.authorAmaral, C
dc.contributor.authorSerrano, I
dc.contributor.authorOliveira, MJ
dc.contributor.authorSackstein, R
dc.contributor.authorVideira, P
dc.date.accessioned2022-01-04T11:28:45Z
dc.date.available2022-01-04T11:28:45Z
dc.date.issued2018
dc.description.abstractBreast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLeX/A ), and α-1,3/4-fucosyltransferases (FUTs) in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E-selectin, initiating tumor extravasation. However, their role in breast carcinogenesis is still unknown. Here, we aimed to define the contribution of the fucosylated structures, including sLeX/A , to cell adhesion, cell signaling, and cell proliferation in invasive ductal carcinomas (IDC), the most frequent type of breast cancer. We first analyzed expression of E-selectin ligands in IDC tissue and established primary cell cultures from the tissue. We observed strong reactivity with E-selectin and anti-sLeX/A antibodies in both IDC tissue and cell lines, and expression of α-1,3/4 FUTs FUT4, FUT5, FUT6, FUT10, and FUT11. To further assess the role of fucosylation in IDC biology, we immortalized a primary IDC cell line with human telomerase reverse transcriptase to create the 'CF1_T cell line'. Treatment with 2-fluorofucose (2-FF), a fucosylation inhibitor, completely abrogated its sLeX/A expression and dramatically reduced adherence of CF1_T cells to E-selectin under hemodynamic flow conditions. In addition, 2-FF-treated CF1_T cells showed a reduced migratory ability, as well as decreased cell proliferation rate. Notably, 2-FF treatment lowered the growth factor expression of CF1_T cells, prominently for FGF2, vascular endothelial growth factor, and transforming growth factor beta, and negatively affected activation of signal-regulating protein kinases 1 and 2 and p38 mitogen-activated protein kinase signaling pathways. These data indicate that fucosylation licenses several malignant features of IDC, such as cell adhesion, migration, proliferation, and growth factor expression, contributing to tumor progression.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMol Oncol. 2018 May;12(5):579-593.pt_PT
dc.identifier.doi10.1002/1878-0261.12163.pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/3949
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.subjectHSJ ANPATpt_PT
dc.subjectAdultpt_PT
dc.subjectAgedpt_PT
dc.subjectFemalept_PT
dc.subjectHumanspt_PT
dc.subjectBreast Neoplasms / enzymology*pt_PT
dc.subjectMiddle Agedpt_PT
dc.subjectBreast Neoplasms / pathologypt_PT
dc.subjectCarcinoma, Ductal, Breast / enzymology*pt_PT
dc.subjectCarcinoma, Ductal, Breast / pathologypt_PT
dc.subjectCell Adhesion / drug effectspt_PT
dc.subjectCell Line, Tumorpt_PT
dc.subjectCell Proliferation / drug effectspt_PT
dc.subjectE-Selectin / geneticspt_PT
dc.subjectE-Selectin / metabolism*pt_PT
dc.subjectFucose / analogs & derivativespt_PT
dc.subjectFucose / pharmacologypt_PT
dc.subjectFucosyltransferases / antagonists & inhibitors*pt_PT
dc.subjectLigandspt_PT
dc.subjectMAP Kinase Signaling System / drug effectspt_PT
dc.subjectNeoplasm Invasivenesspt_PT
dc.subjectOligosaccharides / metabolism*pt_PT
dc.subjectPrimary Cell Culturept_PT
dc.subjectSialyl Lewis X Antigenpt_PT
dc.subjectp38 Mitogen-Activated Protein Kinases / geneticspt_PT
dc.subjectp38 Mitogen-Activated Protein Kinases / metabolism*pt_PT
dc.titleInhibition of Fucosylation in Human Invasive Ductal Carcinoma Reduces E-Selectin Ligand Expression, Cell Proliferation, and ERK1/2 and p38 MAPK Activationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage593pt_PT
oaire.citation.startPage579pt_PT
oaire.citation.titleMolecular Oncologypt_PT
oaire.citation.volume12pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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