Journal
STEM CELLS
Volume 31, Issue 9, Pages 1992-2002Publisher
WILEY-BLACKWELL
DOI: 10.1002/stem.1459
Keywords
Airway epithelium; Basal cells; Gene expression; Lung cancer; Stem cells
Categories
Funding
- Starr Foundation/Starr Cancer Consortium
- Parker B. Francis Foundation
- [P50 HL084936]
- [R01 HL107882]
- [UL1-RR024996]
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Activation of the human embryonic stem cell (hESC) signature genes has been observed in various epithelial cancers. In this study, we found that the hESC signature is selectively induced in the airway basal stem/progenitor cell population of healthy smokers (BC-S), with a pattern similar to that activated in all major types of human lung cancer. We further identified a subset of 6 BC-S hESC genes, whose coherent overexpression in lung adenocarcinoma (AdCa) was associated with reduced lung function, poorer differentiation grade, more advanced tumor stage, remarkably shorter survival, and higher frequency of TP53 mutations. BC-S shared with hESC and a considerable subset of lung carcinomas a common TP53 inactivation molecular pattern which strongly correlated with the BC-S hESC gene expression. These data provide transcriptome-based evidence that smoking-induced reprogramming of airway BC toward the hESC-like phenotype might represent a common early molecular event in the development of aggressive lung carcinomas in humans. Stem Cells2013;31:1992-2002
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