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NF-κB-induced KIAA1199 promotes survival through EGFR signalling

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  • Kateryna Shostak

    (Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium)

  • Xin Zhang

    (Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium)

  • Pascale Hubert

    (Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    Laboratory of Experimental Pathology, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    GIGA-Cancer, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium)

  • Serkan Ismail Göktuna

    (Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium)

  • Zheshen Jiang

    (Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium)

  • Iva Klevernic

    (Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium)

  • Julien Hildebrand

    (Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium)

  • Patrick Roncarati

    (Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    Laboratory of Experimental Pathology, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    GIGA-Cancer, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium)

  • Benoit Hennuy

    (Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    GIGA Transcriptomics Facility, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium)

  • Aurélie Ladang

    (Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium)

  • Joan Somja

    (Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    Laboratory of Experimental Pathology, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    GIGA-Cancer, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium)

  • André Gothot

    (Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    GIGA-Infection, Immunity and Inflammation, University of Liege, CHU, Sart-Tilman, Liege 4000, Belgium)

  • Pierre Close

    (Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium)

  • Philippe Delvenne

    (Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    Laboratory of Experimental Pathology, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    GIGA-Cancer, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium)

  • Alain Chariot

    (Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium
    Walloon Excellence in Life Sciences and Biotechnology (WELBIO) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium)

Abstract

Constitutive activation of EGFR- and NF-κB-dependent pathways is a hallmark of cancer, yet signalling proteins that connect both oncogenic cascades are poorly characterized. Here we define KIAA1199 as a BCL-3- and p65-dependent gene in transformed keratinocytes. KIAA1199 expression is enhanced on human papillomavirus (HPV) infection and is aberrantly expressed in clinical cases of cervical (pre)neoplastic lesions. Mechanistically, KIAA1199 binds Plexin A2 and protects from Semaphorin 3A-mediated cell death by promoting EGFR stability and signalling. Moreover, KIAA1199 is an EGFR-binding protein and KIAA1199 deficiency impairs EGF-dependent Src, MEK1 and ERK1/2 phosphorylations. Therefore, EGFR stability and signalling to downstream kinases requires KIAA1199. As such, KIAA1199 promotes EGF-mediated epithelial–mesenchymal transition (EMT). Taken together, our data define KIAA1199 as an oncogenic protein induced by HPV infection and constitutive NF-κB activity that transmits pro-survival and invasive signals through EGFR signalling.

Suggested Citation

  • Kateryna Shostak & Xin Zhang & Pascale Hubert & Serkan Ismail Göktuna & Zheshen Jiang & Iva Klevernic & Julien Hildebrand & Patrick Roncarati & Benoit Hennuy & Aurélie Ladang & Joan Somja & André Goth, 2014. "NF-κB-induced KIAA1199 promotes survival through EGFR signalling," Nature Communications, Nature, vol. 5(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6232
    DOI: 10.1038/ncomms6232
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