Inhibition of CK2α down-regulates Notch1 signalling in lung cancer cells

Authors

  • Shulin Zhang,

    1. Thoracic Oncology Laboratory, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA
    2. Department of Surgical Oncology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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    • These authors contributed equally to this work.
  • Hao Long,

    1. Lung Cancer Institute, Sun Yat-sen University, Guangzhou, China
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    • These authors contributed equally to this work.
  • Yi-Lin Yang,

    1. Thoracic Oncology Laboratory, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA
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  • Yucheng Wang,

    1. Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA
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  • David Hsieh,

    1. Thoracic Oncology Laboratory, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA
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  • Weiming Li,

    1. Department of Surgical Oncology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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  • Alfred Au,

    1. Tissue Core, Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA
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  • Hubert J. Stoppler,

    1. Tissue Core, Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA
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  • Zhidong Xu,

    1. Thoracic Oncology Laboratory, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA
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  • David M. Jablons,

    1. Thoracic Oncology Laboratory, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA
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  • Liang You

    Corresponding author
    • Thoracic Oncology Laboratory, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA
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Correspondence to: Liang YOU, Thoracic Oncology Laboratory, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA

Campus Box 1724, 2340 Sutter Street, N261, San Francisco, CA 94143, USA

Tel: 415-476-6906

Fax: 415-514-1074

E-mail: Liang.You@ucsfmedctr.org

Abstract

Protein kinase CK2 is frequently elevated in a variety of human cancers. The Notch1 signalling pathway has been implicated in stem cell maintenance and its aberrant activation has been shown in several types of cancer including lung cancer. Here, we show, for the first time, that CK2α is a positive regulator of Notch1 signalling in lung cancer cell lines A549 and H1299. We found that Notch1 protein level was reduced after CK2α silencing. Down-regulation of Notch1 transcriptional activity was demonstrated after the silencing of CK2α in lung cancer cells. Furthermore, small-molecule CK2α inhibitor CX-4945 led to a dose-dependent inhibition of Notch1 transcriptional activity. Conversely, forced overexpression of CK2α resulted in an increase in Notch1 transcriptional activity. Finally, the inhibition of CK2α led to a reduced proportion of stem-like CD44 + /CD24− cell population. Thus, we report that the inhibition of CK2α down-regulates Notch1 signalling and subsequently reduces a cancer stem-like cell population in human lung cancer cells. Our data suggest that CK2α inhibitors may be beneficial to the lung cancer patients with activated Notch1 signalling.

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