These authors contributed equally to this work.
Inhibition of CK2α down-regulates Notch1 signalling in lung cancer cells
Article first published online: 8 MAY 2013
© 2013 The Authors. Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Cellular and Molecular Medicine
Volume 17, Issue 7, pages 854–862, July 2013
How to Cite
Zhang, S., Long, H., Yang, Y.-L., Wang, Y., Hsieh, D., Li, W., Au, A., Stoppler, H. J., Xu, Z., Jablons, D. M. and You, L. (2013), Inhibition of CK2α down-regulates Notch1 signalling in lung cancer cells. Journal of Cellular and Molecular Medicine, 17: 854–862. doi: 10.1111/jcmm.12068
- Issue published online: 24 JUL 2013
- Article first published online: 8 MAY 2013
- Manuscript Accepted: 24 MAR 2013
- Manuscript Received: 25 NOV 2012
- NIH. Grant Number: R01 CA140654-01A1
- CD44 + /CD24−;
- cancer stem cell;
- lung cancer
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.