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The Wilms’ tumour suppressor Wt1 is a major regulator of tumour angiogenesis and progression

Author

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  • Kay-Dietrich Wagner

    (Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, University of Nice Sophia-Antipolis)

  • Julien Cherfils-Vicini

    (Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, University of Nice Sophia-Antipolis)

  • Naoki Hosen

    (Osaka University Graduate School of Medicine)

  • Peter Hohenstein

    (The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK)

  • Eric Gilson

    (Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, University of Nice Sophia-Antipolis
    CHU Nice)

  • Nicholas D. Hastie

    (MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Jean-François Michiels

    (Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, University of Nice Sophia-Antipolis
    CHU Nice)

  • Nicole Wagner

    (Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, University of Nice Sophia-Antipolis)

Abstract

Angiogenesis, activation of metastasis and avoidance of immune destruction are important for cancer progression. These biological capabilities are, apart from cancer cells, mediated by different cell types, including endothelial, haematopoietic progenitor and myeloid-derived suppressor cells. We show here that all these cell types frequently express the Wilms’ tumour suppressor Wt1, which transcriptionally controls expression of Pecam-1 (CD31) and c-kit (CD117). Inducible conditional knockout of Wt1 in endothelial, haematopoietic and myeloid-derived suppressor cells is sufficient to cause regression of tumour vascularization and an enhanced immune response, leading to decreased metastasis, regression of established tumours and enhanced survival. Thus, Wt1 is an important regulator of cancer growth via modulation of tumour vascularization, immune response and metastasis formation.

Suggested Citation

  • Kay-Dietrich Wagner & Julien Cherfils-Vicini & Naoki Hosen & Peter Hohenstein & Eric Gilson & Nicholas D. Hastie & Jean-François Michiels & Nicole Wagner, 2014. "The Wilms’ tumour suppressor Wt1 is a major regulator of tumour angiogenesis and progression," Nature Communications, Nature, vol. 5(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6852
    DOI: 10.1038/ncomms6852
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