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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Enhanced Tumorigenic Potential of Colorectal Cancer Cells by Extracellular Sulfatases

Texto completo
Autor(es):
Vicente, Carolina M. [1] ; Lima, Marcelo A. [1, 2] ; Yates, Edwin A. [1, 2] ; Nader, Helena B. [1] ; Toma, Leny [1]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Univ Fed Sao Paulo, Dept Bioquim, Disciplina Biol Mol, BR-04044020 Sao Paulo - Brazil
[2] Univ Liverpool, Inst Integrat Biol, Dept Biochem, Liverpool L69 3BX, Merseyside - England
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: MOLECULAR CANCER RESEARCH; v. 13, n. 3, p. 510-523, MAR 2015.
Citações Web of Science: 9
Resumo

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. (AU)

Processo FAPESP: 12/50024-0 - Papel dos proteoglicanos na biologia do cancer coloretal e de prostata humanos:um estudo in vitro do seu microambiente tumoral.
Beneficiário:Leny Toma
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 09/52430-3 - Microscopia laser aplicada na biologia celular e molecular
Beneficiário:Helena Bonciani Nader
Linha de fomento: Auxílio à Pesquisa - Regular