| First Author | Giangreco A | Year | 2012 |
| Journal | J Pathol | Volume | 226 |
| Issue | 4 | Pages | 575-87 |
| PubMed ID | 22081448 | Mgi Jnum | J:181809 |
| Mgi Id | MGI:5314201 | Doi | 10.1002/path.3962 |
| Citation | Giangreco A, et al. (2012) beta-Catenin determines upper airway progenitor cell fate and preinvasive squamous lung cancer progression by modulating epithelial-mesenchymal transition. J Pathol 226(4):575-87 |
| abstractText | 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 beta-catenin signalling regulates basal progenitor cell fate and subsequent SCC progression. In a cohort of preinvasive SCCs we established that elevated basal cell beta-catenin signalling is positively associated with increased disease severity, epithelial proliferation and reduced intercellular adhesiveness. We demonstrate that transgene-mediated beta-catenin inhibition within keratin 14-expressing basal cells delayed normal airway repair while basal cell-specific beta-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 beta-catenin activation and E-cadherin inhibition, and mirrored our findings in preinvasive SCCs. Overall, the data show that airway basal cell beta-catenin determines cell fate and its mis-expression is associated with the development of human lung cancer. |
