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http://purl.uniprot.org/citations/20725905http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20725905http://www.w3.org/2000/01/rdf-schema#comment"

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Heparan sulfate proteoglycans (HSPGs) act as coreceptors or storage sites for growth factors and cytokines such as fibroblast growth factor and Wnts. Glypican 3 (GPC3) is the most highly expressed HSPG in hepatocellular carcinoma (HCC). Sulfatase 2 (SULF2), an enzyme with 6-O-desulfatase activity on HSPGs, is up-regulated in 60% of primary HCCs and is associated with a worse prognosis. We have previously shown that the oncogenic effect of SULF2 in HCC may be mediated in part through up-regulation of GPC3. Here we demonstrate that GPC3 stimulates the Wnt/β-catenin pathway and mediates the oncogenic function of SULF2 in HCC. Wnt signaling in vitro and in vivo was assessed in SULF2-negative Hep3B HCC cells transfected with SULF2 and in SULF2-expressing Huh7 cells transfected with short hairpin RNA targeting SULF2. The interaction between GPC3, SULF2, and Wnt3a was assessed by coimmunoprecipitation and flow cytometry. β-catenin-dependent transcriptional activity was assessed with the TOPFLASH (T cell factor reporter plasmid) luciferase assay. In HCC cells, SULF2 increased cell surface GPC3 and Wnt3a expression, stabilized β-catenin, and activated T cell factor transcription factor activity and expression of the Wnt/β-catenin target gene cyclin D1. Opposite effects were observed in SULF2-knockdown models. In vivo, nude mouse xenografts established from SULF2-transfected Hep3B cells showed enhanced GPC3, Wnt3a, and β-catenin levels.

Conclusion

Together, these findings identify a novel mechanism mediating the oncogenic function of SULF2 in HCC that includes GPC3-mediated activation of Wnt signaling via the Wnt3a/glycogen synthase kinase 3 beta axis."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.org/dc/terms/identifier"doi:10.1002/hep.23848"xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Li J."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Nakamura I."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Yu C."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Hu C."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Han T."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Roberts L.R."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Adjei A.A."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Moser C.D."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Fernandez-Zapico M.E."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Lai J.P."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Shire A.M."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Isomoto H."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Elsawa S.F."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Aderca I."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Garrity-Park M.M."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Sanderson S.O."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/author"Oseini A.M."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/name"Hepatology"xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/pages"1680-1689"xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/title"The oncogenic effect of sulfatase 2 in human hepatocellular carcinoma is mediated in part by glypican 3-dependent Wnt activation."xsd:string
http://purl.uniprot.org/citations/20725905http://purl.uniprot.org/core/volume"52"xsd:string
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