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- Title
Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer.
- Authors
Shaykhiev, Renat; Wang, Rui; Zwick, Rachel K.; Hackett, Neil R.; Leung, Roland; Moore, Malcolm A. S.; Sima, Camelia S.; Chao, Ion Wa; Downey, Robert J.; Strulovici-Barel, Yael; Salit, Jacqueline; Crystal, Ronald G.
- Abstract
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. S tem C ells 2013;31:1992-2002
- Subjects
LUNG cancer; HEALTH of cigarette smokers; EMBRYONIC stem cells; EPITHELIAL cells; EPITHELIAL tumors; PULMONARY function tests; GENE expression; TUMOR growth
- Publication
Stem Cells, 2013, Vol 31, Issue 9, p1992
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1002/stem.1459