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

Renat Shaykhiev, Rui Wang, Rachel K. Zwick, Neil R. Hackett, Roland Leung, Malcolm A.S. Moore, Camelia S. Sima, Ion Wa Chao, Robert J. Downey, Yael Strulovici-Barel, Jacqueline Salit, Ronald Crystal

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 languageEnglish
Pages (from-to)1992-2002
Number of pages11
JournalStem Cells
Volume31
Issue number9
DOIs
Publication statusPublished - 1 Sep 2013
Externally publishedYes

Fingerprint

Embryonic Stem Cells
Lung Neoplasms
Stem Cells
Lung
Carcinoma
Mutation Rate
Transcriptome
Genes
Human Embryonic Stem Cells
Neoplasms
Smoking
Phenotype
Gene Expression
Survival
Population

Keywords

  • Airway epithelium
  • Basal cells
  • Gene expression
  • Lung cancer
  • Stem cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Shaykhiev, R., Wang, R., Zwick, R. K., Hackett, N. R., Leung, R., Moore, M. A. S., ... Crystal, R. (2013). Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer. Stem Cells, 31(9), 1992-2002. https://doi.org/10.1002/stem.1459

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 journalArticle

Shaykhiev, R, Wang, R, Zwick, RK, Hackett, NR, Leung, R, Moore, MAS, Sima, CS, Chao, IW, Downey, RJ, Strulovici-Barel, Y, Salit, J & Crystal, R 2013, 'Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer', Stem Cells, vol. 31, no. 9, pp. 1992-2002. https://doi.org/10.1002/stem.1459
Shaykhiev R, Wang R, Zwick RK, Hackett NR, Leung R, Moore MAS et al. Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer. Stem Cells. 2013 Sep 1;31(9):1992-2002. https://doi.org/10.1002/stem.1459
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. / Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer. In: Stem Cells. 2013 ; Vol. 31, No. 9. pp. 1992-2002.
@article{54e9ab216c1d4540abaf4c0d8e0da458,
title = "Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer",
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",
keywords = "Airway epithelium, Basal cells, Gene expression, Lung cancer, Stem cells",
author = "Renat Shaykhiev and Rui Wang and Zwick, {Rachel K.} and Hackett, {Neil R.} and Roland Leung and Moore, {Malcolm A.S.} and Sima, {Camelia S.} and Chao, {Ion Wa} and Downey, {Robert J.} and Yael Strulovici-Barel and Jacqueline Salit and Ronald Crystal",
year = "2013",
month = "9",
day = "1",
doi = "10.1002/stem.1459",
language = "English",
volume = "31",
pages = "1992--2002",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press",
number = "9",

}

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

VL - 31

SP - 1992

EP - 2002

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

IS - 9

ER -