Rewiring of human lung cell lineage and mitotic networks in lung adenocarcinomas

Il Jin Kim, David Quigley, Minh D. To, Patrick Pham, Kevin Lin, Brian Jo, Kuang-Yu Jen, Dan Raz, Jae Kim, Jian Hua Mao, David Jablons, Allan Balmain

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Analysis of gene expression patterns in normal tissues and their perturbations in tumours can help to identify the functional roles of oncogenes or tumour suppressors and identify potential new therapeutic targets. Here, gene expression correlation networks were derived from 92 normal human lung samples and patient-matched adenocarcinomas. The networks from normal lung show that NKX2-1 is linked to the alveolar type 2 lineage, and identify PEBP4 as a novel marker expressed in alveolar type 2 cells. Differential correlation analysis shows that the NKX2-1 network in tumours includes pathways associated with glutamate metabolism, and identifies Vaccinia-related kinase (VRK1) as a potential drug target in a tumour-specific mitotic network. We show that VRK1 inhibition cooperates with inhibition of poly (ADP-ribose) polymerase signalling to inhibit growth of lung tumour cells. Targeting of genes that are recruited into tumour mitotic networks may provide a wider therapeutic window than that seen by inhibition of known mitotic genes.

Original languageEnglish (US)
Article number1701
JournalNature Communications
Volume4
DOIs
StatePublished - May 20 2013
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Kim, I. J., Quigley, D., To, M. D., Pham, P., Lin, K., Jo, B., Jen, K-Y., Raz, D., Kim, J., Mao, J. H., Jablons, D., & Balmain, A. (2013). Rewiring of human lung cell lineage and mitotic networks in lung adenocarcinomas. Nature Communications, 4, [1701]. https://doi.org/10.1038/ncomms2660