Secreted antagonists of the Wnt signalling pathway

Kawano, Yoshiaki; Kypta, Robert M.

doi:10.1242/jcs.00623

Cited by 1,433 publications

(1,317 citation statements)

References 77 publications

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“…Secreted Frizzled-related protein 2 (sFRP2) binds to Wnt proteins and acts as a negative regulator of Wnt signaling (Kawano and Kypta, 2003). DU145 cells were allowed to migrate in scratch-wound cultures, resulting in wound closure after 24 h, and the migration of DU145 cells in scratch-wound cultures was inhibited by the addition of sFRP2 conditioned medium (CM) (Figure 3e).…”

Section: Immunohistochemical Analysis Of Wnt5a In Pca Tissuesmentioning

confidence: 99%

Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase

et al. 2010

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Wnt5a is a representative ligand that activates the b-catenin-independent pathway in Wnt signaling. Although it has been reported that abnormal activation of the Wnt/ b-catenin-dependent pathway is often observed in human prostate cancer, the involvement of the b-catenin-independent pathway in this cancer is unclear. Abnormal expression of Wnt5a and b-catenin was observed in 27 (28%) and 49 (50%) of 98 prostate cancer cases, respectively, by immunohistochemical analyses. Simultaneous expression of Wnt5a and b-catenin was observed in only five cases, suggesting their exclusive expression. The positive detection of Wnt5a was correlated with high Gleason scores and biochemical relapse of prostate cancer, but that of b-catenin was not. Knockdown and overexpression of Wnt5a in human prostate cancer cell lines reduced and stimulated, respectively, their invasion activities, and the invasion activity required Frizzled2 and Ror2 as Wnt receptors. Wnt5a activated Jun-N-terminal kinase through protein kinase D (PKD) and the inhibition of PKD suppressed Wnt5a-dependent cell migration and invasion. In addition, Wnt5a induced the expression of metalloproteinase-1 through the recruitment of JunD to its promoter region. These results suggest that Wnt5a promotes the aggressiveness of prostate cancer and that its expression is involved in relapse after prostatectomy.

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Section: Immunohistochemical Analysis Of Wnt5a In Pca Tissuesmentioning

confidence: 99%

Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase

et al. 2010

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“…Wnts are subject to negative and positive regulation by a wide range on effectors that act either intracellularly to modulate components of the signal transduction machinery, or extracellularly to modulate ligand receptor interactions. Five families of extracellular Wnt antagonists are currently known (Kawano and Kypta, 2003), the secreted frizzled-related protein (sFRP), Wnt inhibitory factor 1 (Wif1), Xenopus Cerberus, Wise and the Dickkopf (Dkk) family of secreted proteins, and the latter will be reviewed here.…”

Section: Introductionmentioning

confidence: 99%

Function and biological roles of the Dickkopf family of Wnt modulators

2006

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“…Interaction of Wnt ligands with the Frizzled receptors is enhanced by heparan sulfate glycosaminoglycans controlling Wnt diffusion at the cell surface (Mikels and Nusse, 2006) or inhibited by several families of extracellular antagonists (Kawano and Kypta, 2003;Bovolenta et al, 2008). Members of the Dickkopf (DKK) family antagonize canonical signaling by binding to LRP5/6, thus disrupting the Wnt-induced Frizzled-LRP5/6 complex (MacDonald et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Blocking Wnt signaling by SFRP-like molecules inhibits in vivo cell proliferation and tumor growth in cells carrying active β-catenin

et al. 2010

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Constitutive activation of Wnt/b-catenin signaling in cancer results from mutations in pathway components, which frequently coexist with autocrine Wnt signaling or epigenetic silencing of extracellular Wnt antagonists. Among the extracellular Wnt inhibitors, the secreted frizzled-related proteins (SFRPs) are decoy receptors that contain soluble Wnt-binding frizzled domains. In addition to SFRPs, other endogenous molecules harboring frizzled motifs bind to and inhibit Wnt signaling. One of such molecules is V3Nter, a soluble SFRP-like frizzled polypeptide that binds to Wnt3a and inhibits Wnt signaling and expression of the b-catenin target genes cyclin D1 and c-myc. V3Nter is derived from the cell surface extracellular matrix component collagen XVIII. Here, we used HCT116 human colon cancer cells carrying the DS45 activating mutation in one of the alleles of b-catenin to show that V3Nter and SFRP-1 decrease baseline and Wnt3a-induced b-catenin stabilization. Consequently, V3Nter reduces the growth of human colorectal cancer xenografts by specifically controlling cell proliferation and cell cycle progression, without affecting angiogenesis or apoptosis, as shown by decreased

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Secreted antagonists of the Wnt signalling pathway

Cited by 1,433 publications

References 77 publications

Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase

Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase

Function and biological roles of the Dickkopf family of Wnt modulators

Blocking Wnt signaling by SFRP-like molecules inhibits in vivo cell proliferation and tumor growth in cells carrying active β-catenin

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