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

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21 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

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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., Sima, C. S., Chao, I. W., Downey, R. J., 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, 31(9), 1992-2002. https://doi.org/10.1002/stem.1459