Enhanced Tumorigenic Potential of Colorectal Cancer Cells by Extracellular Sulfatases

Enhanced Tumorigenic Potential of Colorectal Cancer Cells by Extracellular Sulfatases

Author Vicente, Carolina M. Autor UNIFESP Google Scholar
Lima, Marcelo A. Autor UNIFESP Google Scholar
Yates, Edwin A. Autor UNIFESP Google Scholar
Nader, Helena B. Autor UNIFESP Google Scholar
Toma, Leny Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Liverpool
Abstract Heparan 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.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2012/50024-0
FAPESP: 2009/52430-3
FAPESP: 2012/52426-3
Date 2015-03-01
Published in Molecular Cancer Research. Philadelphia: Amer Assoc Cancer Research, v. 13, n. 3, p. 510-523, 2015.
ISSN 1541-7786 (Sherpa/Romeo, impact factor)
Publisher Amer Assoc Cancer Research
Extent 510-523
Origin http://dx.doi.org/10.1158/1541-7786.MCR-14-0372
Access rights Closed access
Type Article
Web of Science ID WOS:000351223800012
URI http://repositorio.unifesp.br/handle/11600/38859

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