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

Author

Listed:
  • Il-Jin Kim

    (Thoracic Oncology Laboratory, University of California, San Francisco, 2340 Sutter street
    Helen Diller Family Cancer Center, University of California, San Francisco, 1450 3rd street)

  • David Quigley

    (Helen Diller Family Cancer Center, University of California, San Francisco, 1450 3rd street)

  • Minh D. To

    (Thoracic Oncology Laboratory, University of California, San Francisco, 2340 Sutter street
    Helen Diller Family Cancer Center, University of California, San Francisco, 1450 3rd street)

  • Patrick Pham

    (Thoracic Oncology Laboratory, University of California, San Francisco, 2340 Sutter street)

  • Kevin Lin

    (Helen Diller Family Cancer Center, University of California, San Francisco, 1450 3rd street)

  • Brian Jo

    (Helen Diller Family Cancer Center, University of California, San Francisco, 1450 3rd street)

  • Kuang-Yu Jen

    (Helen Diller Family Cancer Center, University of California, San Francisco, 1450 3rd street)

  • Dan Raz

    (Thoracic Oncology Laboratory, University of California, San Francisco, 2340 Sutter street)

  • Jae Kim

    (Thoracic Oncology Laboratory, University of California, San Francisco, 2340 Sutter street)

  • Jian-Hua Mao

    (Lawrence Berkeley National Laboratory (LBNL), 1 Cyclotron road)

  • David Jablons

    (Thoracic Oncology Laboratory, University of California, San Francisco, 2340 Sutter street
    Helen Diller Family Cancer Center, University of California, San Francisco, 1450 3rd street)

  • Allan Balmain

    (Helen Diller Family Cancer Center, University of California, San Francisco, 1450 3rd street
    University of California, San Francisco, 600 16th street)

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.

Suggested Citation

  • 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, 2013. "Rewiring of human lung cell lineage and mitotic networks in lung adenocarcinomas," Nature Communications, Nature, vol. 4(1), pages 1-11, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2660
    DOI: 10.1038/ncomms2660
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