Molecular Cloning and Characterization of WNT3A and WNT14 Clustered in Human Chromosome 1q42 Region

Saitoh, Tetsuroh; Hirai, Momoki; Katoh, Masaru

doi:10.1006/bbrc.2001.5105

Cited by 27 publications

(20 citation statements)

References 31 publications

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“…As a control, duplicate cDNA synthesis reactions were done for each experiment without the addition of reverse transcriptase. Different pairs of gene-specific primers (37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51) were used for PCR analysis, and in all cases 30 cycles of amplification were done.…”

Section: Methodsmentioning

confidence: 99%

Glypican-3 Promotes the Growth of Hepatocellular Carcinoma by Stimulating Canonical Wnt Signaling

et al. 2005

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Glypican-3 (GPC3) is a heparan sulfate proteoglycan that is bound to the cell membrane by a glycosyl-phosphatidylinositol anchor. GPC3 is expressed by most hepatocellular carcinomas but not by normal hepatocytes and benign liver lesions. We report here that GPC3 stimulates the in vitro and in vivo growth of hepatocellular carcinoma cells by increasing autocrine/paracrine canonical Wnt signaling. Coimmunoprecipitation experiments showed that GPC3 is able to form complexes with Wnts, and cell-binding assays indicated that GPC3-expressing cells have an increased capacity to bind Wnt. Collectively, these results suggest that GPC3 stimulates Wnt activity by facilitating the interaction of this polypeptide with its signaling receptors. Surprisingly, in contrast to the current model that proposes that Wnt-glypican binding is mediated by the heparan sulfate chains, we found that the nonglycanated GPC3 core protein can form complexes with Wnts. Furthermore, we showed that the glycosaminoglycan chains are not required for the stimulatory effect on Wnt signaling and hepatocellular carcinoma growth. (Cancer Res 2005; 65(14): 6245-54)

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Section: Methodsmentioning

confidence: 99%

Glypican-3 Promotes the Growth of Hepatocellular Carcinoma by Stimulating Canonical Wnt Signaling

et al. 2005

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“…Several mRNAs encoding Wnt ligands and FZD receptors were detected in human term placenta [9][10][11][12][13]. In addition, endometrial expression of Wnt3 and Dickkopf-1 (Dkk1), which inhibits canonical Wnt signalling by disrupting binding of LRP-5/6 to the Wnt/FZD complex, was observed [14], suggesting paracrine mechanisms regulating implantation and/or trophoblast invasion.…”

Section: Introductionmentioning

confidence: 99%

Complex Expression Pattern of Wnt Ligands and Frizzled Receptors in Human Placenta and its Trophoblast Subtypes

et al. 2007

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Canonical Wingless (Wnt) signalling provoked by exogenous and endogenous Wnt ligands was recently shown to play a crucial role in the invasive differentiation of human trophoblasts. To gain insights into the expression pattern of the developmental regulators, we analysed all human Wnt ligands and their frizzled (FZD) receptors in the human placenta and different trophoblast model systems using semi-quantitative PCR. Fourteen out of 19 Wnt ligands and 8 out of 10 FZD receptors were detectable in placental tissues, however, expression patterns varied with gestational age and between different trophoblast subtypes suggesting cell-specific functions. Besides Wnt ligands acting through the canonical pathway, non-canonical ligands such as Wnt-5a, which may also activate alternative Wnt signalling pathways or inhibit canonical Wnt signalling, could be identified. Western blot analyses revealed secretion of Wnt-5a from primary trophoblast cultures and trophoblastic cell lines. To evaluate the potential role of Wnt-5a, SGHPL-5 trophoblast cells were transfected with luciferase reporter plasmids harbouring eight T-cell factor (TCF) DNArecognition sequences which are exclusively activated through the canonical Wnt signalling pathway. Luciferase assays revealed that Wnt-3a-induced reporter activity was repressed by recombinant Wnt-5a indicating an antagonistic role in trophoblasts. The data suggest that a complex network of Wnt ligands and FZD receptors may regulate developmental processes of the human placenta.

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“…34 In addition, several mRNAs encoding Wnt ligands are expressed in the human placenta. [35][36][37][38][39] Therefore, we studied expression and localization of LEF-1/TCFs in the differentiating anchoring villus and investigated the influence of Wntdependent activation of these factors on trophoblast proliferation, migration, and invasion. Moreover, we examined nuclear expression of ␤-catenin in normal placentas and tissues from CHM.…”

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confidence: 99%

Activation of the Canonical Wingless/T-Cell Factor Signaling Pathway Promotes Invasive Differentiation of Human Trophoblast

Pollheimer

Loregger

Sonderegger

et al. 2006

The American Journal of Pathology

176

192

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The molecular mechanisms governing invasive differentiation of human trophoblasts remain largely elusive. Here, we investigated the role of Wnt-␤-catenin-T-cell factor (TCF) signaling in this process. Reverse transcriptase-polymerase chain reaction and Western blot analyses demonstrated expression of Wnt ligands, frizzled receptors, LRP-6, and TCF-3/4 transcription factors in total placenta and different trophoblast cell models. Immunohistochemistry of placental tissues and differentiating villous explant cultures showed that expression of TCF-3/4 strongly increased in invading trophoblasts. Some of these cells also accumulated dephosphorylated ␤-catenin in the nucleus. Wnt3A treatment of primary cytotrophoblasts and SGHPL-5 cells induced activity of TCF-luciferase reporters. Accordingly, the ligand provoked interaction of TCF-3/4 with ␤-catenin as assessed in electrophoretic mobility shift assays (EMSAs) and upregulation of Wnt/TCF target genes as observed by Western blot analyses. Wnt3A stimulated trophoblast migration and invasion through Matrigel, which could be blocked by addition of Dickkopf-1, mediating inhibition of canonical Wnt signaling. Dickkopf-1 also reduced basal migration, invasion, and proliferation of cytotrophoblasts, suggesting expression of endogenous Wnt ligand(s). Immunohistochemistry revealed that the percentage of extravillous trophoblasts containing nuclear ␤-catenin was significantly higher in placentas of complete hydatidiform mole pregnancies as compared to normal placentas. Thus, canonical Wnt signaling may promote invasive trophoblast differentiation, and exaggerated activation of the pathway could contribute to trophoblastic hyperplasia and local invasion.

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Molecular Cloning and Characterization of WNT3A and WNT14 Clustered in Human Chromosome 1q42 Region

Cited by 27 publications

References 31 publications

Glypican-3 Promotes the Growth of Hepatocellular Carcinoma by Stimulating Canonical Wnt Signaling

Glypican-3 Promotes the Growth of Hepatocellular Carcinoma by Stimulating Canonical Wnt Signaling

Complex Expression Pattern of Wnt Ligands and Frizzled Receptors in Human Placenta and its Trophoblast Subtypes

Activation of the Canonical Wingless/T-Cell Factor Signaling Pathway Promotes Invasive Differentiation of Human Trophoblast

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