The Kinome of Human Alveolar Type II and Basal Cells, and Its Reprogramming in Lung Cancer

Am J Respir Cell Mol Biol. 2019 Oct;61(4):481-491. doi: 10.1165/rcmb.2018-0283OC.

Abstract

The discovery of mutant tyrosine kinases as oncogenic drivers of lung adenocarcinomas has changed the basic understanding of lung cancer development and therapy. Yet, expressed kinases (kinome) in lung cancer progenitor cells, as well as whether kinase expression and the overall kinome changes or is reprogrammed upon transformation, is incompletely understood. We hypothesized that the kinome differs between lung cancer progenitor cells, alveolar type II cells (ATII), and basal cells (BC) and that their respective kinomes undergo distinct lineage-specific reprogramming to adenocarcinomas and squamous cell carcinomas upon transformation. We performed RNA sequencing on freshly isolated human ATII, BC, and lung cancer cell lines to define the kinome in nontransformed cells and transformed cells. Our studies identified a unique kinome for ATII and BC and changes in their kinome upon transformation to their respective carcinomas.

Keywords: alveolar type II cells; basal cells; kinome; lung adenocarcinoma; lung squamous cell carcinoma.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics
  • Adult Stem Cells / enzymology*
  • Alveolar Epithelial Cells / enzymology*
  • Animals
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / genetics
  • Cell Lineage
  • Cell Transformation, Neoplastic*
  • Cells, Cultured
  • Enzyme Induction
  • Humans
  • Lung / cytology
  • Lung / enzymology*
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics
  • Mice
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplastic Stem Cells / enzymology
  • Protein-Tyrosine Kinases / analysis*
  • Protein-Tyrosine Kinases / biosynthesis
  • Protein-Tyrosine Kinases / genetics
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis
  • Transcriptome

Substances

  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Protein-Tyrosine Kinases