title: Inhibition of CK2α down-regulates Notch1 signalling in lung cancer cells.
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.
authors: Thoracic Oncology Laboratory, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
authors: Shulin
authors: S
authors: Zhang
authors: Hao
authors: H
authors: Long
authors: Yi-Lin
authors: YL
authors: Yang
authors: Yucheng
authors: Y
authors: Wang
authors: David
authors: D
authors: Hsieh
authors: Weiming
authors: W
authors: Li
authors: Alfred
authors: A
authors: Au
authors: Hubert J
authors: HJ
authors: Stoppler
authors: Zhidong
authors: Z
authors: Xu
authors: David M
authors: DM
authors: Jablons
authors: Liang
authors: L
authors: You
mesh_terms: D051927:CD24 Antigen / Q000378:metabolism; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism*; D009287:Naphthyridines / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000166:cytology; D010619:Phenazines; D010641:Phenotype; D034741:RNA, Small Interfering / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D051927:CD24 Antigen; D018960:Hyaluronan Receptors; C497761:NOTCH1 protein, human; D009287:Naphthyridines; D010619:Phenazines; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D004247:DNA; C555142:silmitasertib; D047390:Casein Kinase II
keywords: CD44 + /CD24−; CK2α; Notch1; cancer stem cell; lung cancer
references: Cell Mol Life Sci. 2009 Jun;66(11-12):1858-67
references: 19387548
references: Eur J Cancer. 2007 Mar;43(5):928-34
references: 17267203
references: Clin Cancer Res. 2007 Feb 1;13(3):1019-28
references: 17289898
references: FASEB J. 2003 Mar;17(3):349-68
references: 12631575
references: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
references: 12629218
references: Mol Cell Biochem. 2011 Oct;356(1-2):45-50
references: 21735096
references: Mol Cell Biol. 2002 Jun;22(11):3927-41
references: 11997524
references: Science. 1995 Apr 14;268(5208):225-32
references: 7716513
references: J Pathol. 2011 Mar;223(4):519-30
references: 21294125
references: Ann Surg Oncol. 2010 Jun;17(6):1695-702
references: 20087779
references: Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17761-6
references: 22006338
references: Science. 1999 Apr 30;284(5415):770-6
references: 10221902
references: Cancer Sci. 2010 Nov;101(11):2417-24
references: 20950370
references: PLoS One. 2012;7(6):e38996
references: 22768056
references: Cell Mol Biol Res. 1994;40(5-6):489-99
references: 7735323
references: Clin Exp Metastasis. 2012 Dec;29(8):939-48
references: 22610780
references: Biochim Biophys Acta. 2008 Jan;1784(1):33-47
references: 17931986
references: Dev Biol. 2001 Oct 1;238(1):110-9
references: 11783997
references: Science. 2001 Aug 31;293(5535):1663-6
references: 11533491
references: Blood. 2006 Sep 1;108(5):1698-707
references: 16684960
references: J Biol Chem. 2011 Jun 17;286(24):21372-83
references: 21504905
references: Oncogene. 2010 Apr 29;29(17):2488-98
references: 20154720
references: Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22293-8
references: 20007775
references: FEBS Lett. 2001 May 4;496(1):44-8
references: 11343704
references: Biochim Biophys Acta. 2010 Mar;1804(3):499-504
references: 19665589
references: J Med Chem. 2011 Jan 27;54(2):635-54
references: 21174434
references: Expert Rev Anticancer Ther. 2011 Apr;11(4):533-40
references: 21504320
references: Mol Cell Biochem. 2011 Oct;356(1-2):37-43
references: 21755459
references: Blood. 2010 Oct 14;116(15):2724-31
references: 20660292
references: PLoS One. 2010 Nov 19;5(11):e14062
references: 21124918
references: Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):23-8
references: 9874765
references: Nucleic Acids Res. 2003 Jul 1;31(13):3635-41
references: 12824383
references: Mol Cancer Ther. 2010 Dec;9(12):3126-36
references: 20940321
references: Cancer Res. 1999 Mar 1;59(5):1146-51
references: 10070976
references: Mol Cancer Res. 2011 Jul;9(7):834-44
references: 21665937
references: Stem Cell Rev. 2007 Jan;3(1):30-8
references: 17873379
references: Int J Oncol. 2006 Mar;28(3):685-93
references: 16465374
references: Adv Enzyme Regul. 2008;48:179-87
references: 18492491
references: Mol Cell Biol. 2003 Feb;23(3):908-15
references: 12529396
references: Cell Mol Life Sci. 2009 Jun;66(11-12):1850-7
references: 19387549
references: Mol Cell Biochem. 2008 Sep;316(1-2):91-7
references: 18574673