Advanced search
2 files | 4.19 MB

The proinvasive activity of Wnt-2 is mediated through a noncanonical Wnt pathway coupled to GSK-3β and c-Jun/AP-1 signaling

(2004) FASEB JOURNAL. 18(13). p.144-146
Author
Organization
Abstract
Inappropriate activation of the Wnt/APC/beta-catenin signaling pathways plays a critical role at early stages in a variety of human cancers. However, their respective implication in tumor cell invasion is still hypothetical. Here, we show that two activators of the canonical Wnt/beta-catenin transcription pathway, namely Dvl-2, the Axin 501-560 fragment binding glycogen synthase kinase -3beta (GSK-3beta), and the negative Wnt regulator wt-Axin did not alter cell invasion into type I collagen. In addition, both Dvl-2 and Axin 501-560 exerted a permissive action on the proinvasive activity of HGF and intestinal trefoil factor. Upstream activation of Wnt signaling by the Wnt-2 and Wnt-3a ligands, stable overexpression of Wnt-2, as well as GSK-3beta inhibition by lithium, SB216763, and GSK-3beta dominant negative forms (K85R and R96E) conferred the invasive phenotype through several proinvasive pathways. Induction of the matrix metalloprotease MMP-7 (matrilysin) gene and protein by Wnt-2 was abolished by inactivation of the AP-1 binding site in the promoter. Accordingly, invasion induced by Wnt-2 was prevented by soluble FRP-3 and FRP-1, sequestration of Gbetagamma subunits, depletion of the GSK-3beta protein by RNA interference, the c-Jun dominant negative mutant TAM67 and was not reversed by wt-Axin. Thus, the proinvasive activity of Wnt-2 is mediated by a noncanonical Wnt pathway using GSK-3beta and the AP-1 oncogene. Our data provide a potential clue for our understanding of the action and crosstalk between Wnt activators and other proinvasive pathways, in relation with matrix substrates and proteases in human cancers.
Keywords
Dvl-2, sFRP-3, axin, trefoil peptides, HGF, Rho GTPases, Rho-kinase, PI3-kinase, GSK-3 beta silencing RNAs, matrilysin, EPIDERMAL-GROWTH-FACTOR, GLYCOGEN-SYNTHASE KINASE-3, CARCINOMA-ASSOCIATED ANTIGEN, PROMOTES CELLULAR INVASION, MAMMARY EPITHELIAL-CELLS, F9 TERATOCARCINOMA CELLS, G-ALPHA-O, BETA-CATENIN, FACTOR-RECEPTOR, TYROSINE PHOSPHORYLATION

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 3.92 MB
  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 271.17 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Le Floch, Nathalie, Christine Rivat, Olivier De Wever, Erik Bruyneel, Marcus Mareel, Trevor Dale, and Christian Gespach. 2004. “The Proinvasive Activity of Wnt-2 Is Mediated Through a Noncanonical Wnt Pathway Coupled to GSK-3β and c-Jun/AP-1 Signaling.” Faseb Journal 18 (13): 144–146.
APA
Le Floch, N., Rivat, C., De Wever, O., Bruyneel, E., Mareel, M., Dale, T., & Gespach, C. (2004). The proinvasive activity of Wnt-2 is mediated through a noncanonical Wnt pathway coupled to GSK-3β and c-Jun/AP-1 signaling. FASEB JOURNAL, 18(13), 144–146.
Vancouver
1.
Le Floch N, Rivat C, De Wever O, Bruyneel E, Mareel M, Dale T, et al. The proinvasive activity of Wnt-2 is mediated through a noncanonical Wnt pathway coupled to GSK-3β and c-Jun/AP-1 signaling. FASEB JOURNAL. 2004;18(13):144–6.
MLA
Le Floch, Nathalie, Christine Rivat, Olivier De Wever, et al. “The Proinvasive Activity of Wnt-2 Is Mediated Through a Noncanonical Wnt Pathway Coupled to GSK-3β and c-Jun/AP-1 Signaling.” FASEB JOURNAL 18.13 (2004): 144–146. Print.
@article{1256566,
  abstract     = {Inappropriate activation of the Wnt/APC/beta-catenin signaling pathways plays a critical role at early stages in a variety of human cancers. However, their respective implication in tumor cell invasion is still hypothetical. Here, we show that two activators of the canonical Wnt/beta-catenin transcription pathway, namely Dvl-2, the Axin 501-560 fragment binding glycogen synthase kinase -3beta (GSK-3beta), and the negative Wnt regulator wt-Axin did not alter cell invasion into type I collagen. In addition, both Dvl-2 and Axin 501-560 exerted a permissive action on the proinvasive activity of HGF and intestinal trefoil factor. Upstream activation of Wnt signaling by the Wnt-2 and Wnt-3a ligands, stable overexpression of Wnt-2, as well as GSK-3beta inhibition by lithium, SB216763, and GSK-3beta dominant negative forms (K85R and R96E) conferred the invasive phenotype through several proinvasive pathways. Induction of the matrix metalloprotease MMP-7 (matrilysin) gene and protein by Wnt-2 was abolished by inactivation of the AP-1 binding site in the promoter. Accordingly, invasion induced by Wnt-2 was prevented by soluble FRP-3 and FRP-1, sequestration of Gbetagamma subunits, depletion of the GSK-3beta protein by RNA interference, the c-Jun dominant negative mutant TAM67 and was not reversed by wt-Axin. Thus, the proinvasive activity of Wnt-2 is mediated by a noncanonical Wnt pathway using GSK-3beta and the AP-1 oncogene. Our data provide a potential clue for our understanding of the action and crosstalk between Wnt activators and other proinvasive pathways, in relation with matrix substrates and proteases in human cancers.},
  author       = {Le Floch, Nathalie and Rivat, Christine and De Wever, Olivier and Bruyneel, Erik and Mareel, Marcus and Dale, Trevor and Gespach, Christian},
  issn         = {0892-6638},
  journal      = {FASEB JOURNAL},
  keywords     = {Dvl-2,sFRP-3,axin,trefoil peptides,HGF,Rho GTPases,Rho-kinase,PI3-kinase,GSK-3 beta silencing RNAs,matrilysin,EPIDERMAL-GROWTH-FACTOR,GLYCOGEN-SYNTHASE KINASE-3,CARCINOMA-ASSOCIATED ANTIGEN,PROMOTES CELLULAR INVASION,MAMMARY EPITHELIAL-CELLS,F9 TERATOCARCINOMA CELLS,G-ALPHA-O,BETA-CATENIN,FACTOR-RECEPTOR,TYROSINE PHOSPHORYLATION},
  language     = {eng},
  number       = {13},
  pages        = {144--146},
  title        = {The proinvasive activity of Wnt-2 is mediated through a noncanonical Wnt pathway coupled to GSK-3β and c-Jun/AP-1 signaling},
  url          = {http://dx.doi.org/10.1096/fj.04-2373fje},
  volume       = {18},
  year         = {2004},
}

Altmetric
View in Altmetric
Web of Science
Times cited: