Open AccessInhibition of CK 2α down‐regulates Notch1 signalling in lung cancer cells
Author(s) -
Zhang Shulin,
Long Hao,
Yang YiLin,
Wang Yucheng,
Hsieh David,
Li Weiming,
Au Alfred,
Stoppler Hubert J.,
Xu Zhidong,
Jablons David M.,
You Liang
Publication year - 2013
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12068
Subject(s) - gene silencing , lung cancer , cancer research , cancer stem cell , population , side population , biology , stem cell , cell , cell growth , cancer , downregulation and upregulation , kinase , cancer cell , regulator , chemistry , microbiology and biotechnology , medicine , biochemistry , genetics , gene , environmental health
Protein kinase CK 2 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 CK 2α is a positive regulator of Notch1 signalling in lung cancer cell lines A549 and H1299. We found that Notch1 protein level was reduced after CK 2α silencing. Down‐regulation of Notch1 transcriptional activity was demonstrated after the silencing of CK 2α in lung cancer cells. Furthermore, small‐molecule CK 2α inhibitor CX ‐4945 led to a dose‐dependent inhibition of Notch1 transcriptional activity. Conversely, forced overexpression of CK 2α resulted in an increase in Notch1 transcriptional activity. Finally, the inhibition of CK 2α led to a reduced proportion of stem‐like CD 44 + / CD 24− cell population. Thus, we report that the inhibition of CK 2α down‐regulates Notch1 signalling and subsequently reduces a cancer stem‐like cell population in human lung cancer cells. Our data suggest that CK 2α inhibitors may be beneficial to the lung cancer patients with activated Notch1 signalling.