No conflicts of interest were declared.
β-Catenin determines upper airway progenitor cell fate and preinvasive squamous lung cancer progression by modulating epithelial–mesenchymal transition†
Article first published online: 17 JAN 2012
Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 226, Issue 4, pages 575–587, March 2012
How to Cite
Giangreco, A., Lu, L., Vickers, C., Teixeira, V. H., Groot, K. R., Butler, C. R., Ilieva, E. V., George, P. J., Nicholson, A. G., Sage, E. K., Watt, F. M. and Janes, S. M. (2012), β-Catenin determines upper airway progenitor cell fate and preinvasive squamous lung cancer progression by modulating epithelial–mesenchymal transition. J. Pathol., 226: 575–587. doi: 10.1002/path.3962
- Issue published online: 2 FEB 2012
- Article first published online: 17 JAN 2012
- Accepted manuscript online: 14 NOV 2011 04:13AM EST
- Manuscript Accepted: 4 NOV 2011
- Manuscript Revised: 3 NOV 2011
- Manuscript Received: 5 AUG 2011
- Re-use of this article is permitted in accordance with the Terms and Conditions set out at . [http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms]
- stem cell;
- lung cancer;
Human lung cancers, including squamous cell carcinoma (SCC) are a leading cause of death and, whilst evidence suggests that basal stem cells drive SCC initiation and progression, the mechanisms regulating these processes remain unknown. In this study we show that β-catenin signalling regulates basal progenitor cell fate and subsequent SCC progression. In a cohort of preinvasive SCCs we established that elevated basal cell β-catenin signalling is positively associated with increased disease severity, epithelial proliferation and reduced intercellular adhesiveness. We demonstrate that transgene-mediated β-catenin inhibition within keratin 14-expressing basal cells delayed normal airway repair while basal cell-specific β-catenin activation increased cell proliferation, directed differentiation and promoted elements of early epithelial-mesenchymal transition (EMT), including increased Snail transcription and reduced E-cadherin expression. These observations are recapitulated in normal human bronchial epithelial cells in vitro following both pharmacological β-catenin activation and E-cadherin inhibition, and mirrored our findings in preinvasive SCCs. Overall, the data show that airway basal cell β-catenin determines cell fate and its mis-expression is associated with the development of human lung cancer. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.