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A monoclonal antibody against KCNK9 K+ channel extracellular domain inhibits tumour growth and metastasis

Author

Listed:
  • Han Sun

    (Johns Hopkins University School of Medicine
    Hugo W. Moser Research Institute at Kennedy Krieger)

  • Liqun Luo

    (Immunotherapy Institute, Fujian Medical University)

  • Bachchu Lal

    (Hugo W. Moser Research Institute at Kennedy Krieger)

  • Xinrong Ma

    (University of Maryland)

  • Lieping Chen

    (Yale University School of Medicine)

  • Christine L. Hann

    (Johns Hopkins University School of Medicine)

  • Amy M. Fulton

    (University of Maryland
    Baltimore Veterans Administration Medical Center)

  • Daniel J. Leahy

    (Johns Hopkins University School of Medicine)

  • John Laterra

    (Johns Hopkins University School of Medicine
    Hugo W. Moser Research Institute at Kennedy Krieger
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Min Li

    (Johns Hopkins University School of Medicine
    Present address: GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA.)

Abstract

Two-pore domain potassium (K2P) channels act to maintain cell resting membrane potential—a prerequisite for many biological processes. KCNK9, a member of K2P family, is implicated in cancer, owing to its overexpression in human tumours and its ability to promote neoplastic cell survival and growth. However, KCNK9’s underlying contributions to malignancy remain elusive due to the absence of specific modulators. Here we describe the development of monoclonal antibodies against the KCNK9 extracellular domain and their functional effects. We show that one antibody (Y4) with the highest affinity binding induces channel internalization. The addition of Y4 to KCNK9-expressing carcinoma cells reduces cell viability and increases cell death. Systemic administration of Y4 effectively inhibits growth of human lung cancer xenografts and murine breast cancer metastasis in mice. Evidence for Y4-mediated carcinoma cell autonomous and immune-dependent cytotoxicity is presented. Our study reveals that antibody-based KCNK9 targeting is a promising therapeutic strategy in KCNK9-expressing malignancies.

Suggested Citation

  • Han Sun & Liqun Luo & Bachchu Lal & Xinrong Ma & Lieping Chen & Christine L. Hann & Amy M. Fulton & Daniel J. Leahy & John Laterra & Min Li, 2016. "A monoclonal antibody against KCNK9 K+ channel extracellular domain inhibits tumour growth and metastasis," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10339
    DOI: 10.1038/ncomms10339
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    Cited by:

    1. Susanne Rinné & Florian Schick & Kirsty Vowinkel & Sven Schütte & Cornelius Krasel & Silke Kauferstein & Martin K.-H. Schäfer & Aytug K. Kiper & Thomas Müller & Niels Decher, 2024. "Potassium channel TASK-5 forms functional heterodimers with TASK-1 and TASK-3 to break its silence," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Marcos Matamoros & Xue Wen Ng & Joshua B. Brettmann & David W. Piston & Colin G. Nichols, 2023. "Conformational plasticity of NaK2K and TREK2 potassium channel selectivity filters," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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