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Suspension survival mediated by PP2A-STAT3-Col XVII determines tumour initiation and metastasis in cancer stem cells

Author

Listed:
  • Chen-Chi Liu

    (Institute of Clinical Medicine, National Yang-Ming University)

  • Shih-Pei Lin

    (Institute of Clinical Medicine, National Yang-Ming University)

  • Han-Shui Hsu

    (Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang-Ming University
    Taipei Veterans General Hospital)

  • Shung-Haur Yang

    (Taipei Veterans General Hospital
    School of Medicine, National Yang-Ming University)

  • Chiu-Hua Lin

    (Institute of Clinical Medicine, National Yang-Ming University)

  • Muh-Hwa Yang

    (Institute of Clinical Medicine, National Yang-Ming University
    Taipei Veterans General Hospital)

  • Mien-Chie Hung

    (Graduate Institute of Cancer Biology, College of Medicine, Center for Molecular Medicine, China Medical University and Hospital
    The University of Texas M.D. Anderson Cancer Center)

  • Shih-Chieh Hung

    (Institute of Clinical Medicine, National Yang-Ming University
    Stem Cell Laboratory, Taipei Veterans General Hospital
    Institute of Biomedical Sciences, Academia Sinica
    Integrative Stem Cell Center, China Medical University Hospital)

Abstract

Targeting tumour-initiating cells (TICs) would lead to new therapies to cure cancer. We previously demonstrated that TICs have the capacity to survive under suspension conditions, while other cells undergo anoikis. Here we show that TICs exhibit increased phosphorylation levels of S727STAT3 because of PP2A inactivation. Collagen 17 gene expression is upregulated in a STAT3-dependent manner, which also stabilizes laminin 5 and engages cells to form hemidesmosome-like junctions in response. Blocking the PP2A-S727STAT3-collagen 17 pathway inhibits the suspension survival of TICs and their ability to form tumours in mice, while activation of the same pathway increases the suspension survival and tumour-initiation capacities of bulk cancer cells. The S727STAT3 phosphorylation levels correlate with collagen 17 expression in colon tumour samples, and correlate inversely with survival. Finally, this signalling axis enhances the ability of TIC to form tumours in mouse models of malignant lung cancer pleural effusion and spontaneous colon cancer metastasis.

Suggested Citation

  • Chen-Chi Liu & Shih-Pei Lin & Han-Shui Hsu & Shung-Haur Yang & Chiu-Hua Lin & Muh-Hwa Yang & Mien-Chie Hung & Shih-Chieh Hung, 2016. "Suspension survival mediated by PP2A-STAT3-Col XVII determines tumour initiation and metastasis in cancer stem cells," Nature Communications, Nature, vol. 7(1), pages 1-19, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11798
    DOI: 10.1038/ncomms11798
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