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. Stem Cells 2013;31:1992-2002
| Original language | English |
|---|---|
| Pages (from-to) | 1992-2002 |
| Number of pages | 11 |
| Journal | Stem Cells |
| Volume | 31 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 1 Sep 2013 |
| Externally published | Yes |
Fingerprint
Keywords
- Airway epithelium
- Basal cells
- Gene expression
- Lung cancer
- Stem cells
ASJC Scopus subject areas
- Molecular Medicine
- Developmental Biology
- Cell Biology
Cite this
Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer. / 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.
In: Stem Cells, Vol. 31, No. 9, 01.09.2013, p. 1992-2002.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer
AU - Shaykhiev, Renat
AU - Wang, Rui
AU - Zwick, Rachel K.
AU - Hackett, Neil R.
AU - Leung, Roland
AU - Moore, Malcolm A.S.
AU - Sima, Camelia S.
AU - Chao, Ion Wa
AU - Downey, Robert J.
AU - Strulovici-Barel, Yael
AU - Salit, Jacqueline
AU - Crystal, Ronald
PY - 2013/9/1
Y1 - 2013/9/1
N2 - 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 Cells 2013;31:1992-2002
AB - 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 Cells 2013;31:1992-2002
KW - Airway epithelium
KW - Basal cells
KW - Gene expression
KW - Lung cancer
KW - Stem cells
UR - http://www.scopus.com/inward/record.url?scp=84885110038&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885110038&partnerID=8YFLogxK
U2 - 10.1002/stem.1459
DO - 10.1002/stem.1459
M3 - Article
C2 - 23857717
AN - SCOPUS:84885110038
VL - 31
SP - 1992
EP - 2002
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 9
ER -