Abstract
The epithelium to mesenchyme transition is thought to play a fundamental role during embryonic development and tumor progression. Loss of cell–cell adhesion and modification of both cell morphology and gene expression are the main events associated with this transition. There is a large amount of evidence suggesting that growth factors can initiate these events. Yet, the connection from growth factor induction to changes in cell adhesion and morphology is largely unknown. To elucidate this connection, we have investigated the action of IGF-II on E-cadherin/β-catenin complex-mediated cell–cell adhesion and on β-catenin/TCF-3 mediated gene expression. We can show that (1) IGF-II induces a rapid epithelium to mesenchymal transition; (2) IGF1R, the receptor for IGF-II, belongs to the same membrane complex as E-cadherin and β-catenin; (3) IGF-II induces a redistribution of β-catenin from the plasma membrane to the nucleus and an intracellular sequestration and degradation of E-cadherin; (4) IGF-II induces the transcription of β-catenin/TCF-3 target genes. Based on the given case of IGF-II and E-cadherin/β-catenin complex, this study reveals the backbone of a cascade connecting growth factor signaling with cell–cell adhesion during EMT.
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Acknowledgements
We wish to thank H Clevers and R Kemler for the Top-Fop flash plasmids, J Camonis for the two-hybrid system kit, W Birchmeier for the TCF-3 antibody, and H Hoschuetzky for the H2Kd antibody. We are grateful to A Ben Ze'ev, M Guvakova, J Salamero, E Surmacz, and A Taddei for helpful discussions. We thank B Boyer, J Jouanneau, I Tratner and AM Vallès for providing comments on the manuscript. This work was supported by grants from Association Française contre les Myopathies (#6864), the Association sur la Recherche contre le Cancer (#9991) and by the Ligue contre le Cancer-Yvelines (GL/MM 298/99). O Morali and R Moore were supported by grants from AFM and FRM, respectively.
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Morali, O., Delmas, V., Moore, R. et al. IGF-II induces rapid β-catenin relocation to the nucleus during epithelium to mesenchyme transition. Oncogene 20, 4942–4950 (2001). https://doi.org/10.1038/sj.onc.1204660
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DOI: https://doi.org/10.1038/sj.onc.1204660
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