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dc.contributor.authorVicente, Carolina M. [UNIFESP]
dc.contributor.authorLima, Marcelo A. [UNIFESP]
dc.contributor.authorYates, Edwin A. [UNIFESP]
dc.contributor.authorNader, Helena B. [UNIFESP]
dc.contributor.authorToma, Leny [UNIFESP]
dc.identifier.citationMolecular Cancer Research. Philadelphia: Amer Assoc Cancer Research, v. 13, n. 3, p. 510-523, 2015.
dc.description.abstractHeparan sulfate endosulfatase-1 and -2 (SULF1 and SULF2) are two important extracellular 6-O-endosulfatases that remove 6-O sulfate groups of N-glucosamine along heparan sulfate (HS) proteoglycan chains often found in the extracellular matrix. the HS sulfation pattern influences signaling events at the cell surface, which are critical for interactions with growth factors and their receptors. SULFs are overexpressed in several types of human tumors, but their role in cancer is still unclear because their molecular mechanism has not been fully explored and understood. To further investigate the functions of these sulfatases in tumorigenesis, stable overexpression models of these genes were generated in the colorectal cancer cells, Caco-2 and HCT-116. Importantly, mimicking overexpression of these sulfatases resulted in increased viability and proliferation, and augmented cell migration. These effects were reverted by shRNA-mediated knockdown of SULF1 or SULF2 and by the addition of unfractionated heparin. Detailed structural analysis of HS from cells overexpressing SULFs showed reduction in the trisulfated disaccharide UA(2S)-GlcNS(6S) and corresponding increase in UA(2S)-GlcNS disaccharide, as well as an unexpected rise in less common disaccharides containing GlcNAc(6S) residues. Moreover, cancer cells transfected with SULFs demonstrated increased Wnt signaling. in summary, SULF1 or SULF2 overexpression contributes to colorectal cancer cell proliferation, migration, and invasion.en
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.publisherAmer Assoc Cancer Research
dc.relation.ispartofMolecular Cancer Research
dc.rightsAcesso restrito
dc.titleEnhanced Tumorigenic Potential of Colorectal Cancer Cells by Extracellular Sulfatasesen
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Liverpool
dc.description.affiliationUniversidade Federal de São Paulo, Universidade Federal de São Paulo, Dept Bioquim, Disciplina Biol Mol, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv Liverpool, Inst Integrat Biol, Dept Biochem, Liverpool L69 3BX, Merseyside, England
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Universidade Federal de São Paulo, Dept Bioquim, Disciplina Biol Mol, BR-04044020 São Paulo, Brazil
dc.description.sponsorshipIDFAPESP: 2012/50024-0
dc.description.sponsorshipIDFAPESP: 2009/52430-3
dc.description.sponsorshipIDFAPESP: 2012/52426-3
dc.description.sourceWeb of Science

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