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

Shulin Zhang1, Hao Long, Yi-Lin Yang

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

Journal of Cellular and Molecular Medicine
|May 9, 2013
PubMed

Insights

Protein kinase CK2 (CK2α) activates Notch1 signaling in lung cancer cells. Inhibiting CK2α reduces Notch1 activity and decreases cancer stem-like cells, suggesting CK2α inhibitors may benefit lung cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Protein kinase CK2 (CK2α) is frequently elevated in human cancers.
  • The Notch1 signaling pathway is crucial for stem cell maintenance and is aberrantly activated in various cancers, including lung cancer.

Purpose of the Study:

  • To investigate the role of CK2α as a regulator of Notch1 signaling in lung cancer.
  • To determine the effect of CK2α inhibition on Notch1 activity and cancer stem-like cell populations.

Main Methods:

  • Silencing of CK2α in lung cancer cell lines (A549, H1299).
  • Treatment with the small-molecule CK2α inhibitor CX-4945.
  • Assessment of Notch1 protein levels, transcriptional activity, and CD44+/CD24- cell population.

Main Results:

  • CK2α silencing reduced Notch1 protein levels and transcriptional activity.
  • CX-4945 inhibited Notch1 transcriptional activity in a dose-dependent manner.
  • CK2α inhibition decreased the proportion of stem-like CD44+/CD24- cells.

Conclusions:

  • CK2α positively regulates Notch1 signaling in human lung cancer cells.
  • Inhibition of CK2α down-regulates Notch1 signaling and reduces cancer stem-like cells.
  • CK2α inhibitors may offer a therapeutic strategy for lung cancer patients with activated Notch1 signaling.
Keywords:
CD44 + /CD24−CK2αNotch1cancer stem celllung cancer

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