Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer.

Publication Type Academic Article
Authors Shaykhiev R, Wang R, Zwick R, Hackett N, Leung R, Moore M, Sima C, Chao I, Downey R, Strulovici-Barel Y, Salit J, Crystal R
Journal Stem Cells
Volume 31
Issue 9
Pagination 1992-2002
Date Published 09/01/2013
ISSN 1549-4918
Keywords Embryonic Stem Cells, Gene Expression Profiling, Lung, Lung Neoplasms, Smoking
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.
DOI 10.1002/stem.1459
PubMed ID 23857717
PubMed Central ID PMC4051142
Back to Top