title: Inhibition of CK2α down-regulates Hedgehog/Gli signaling leading to a reduction of a stem-like side population in human lung cancer cells.
abstract: Protein kinase CK2 is frequently elevated in a variety of human cancers. The Hedgehog (Hh) signaling pathway has been implicated in stem cell maintenance, and its aberrant activation has been indicated in several types of cancer, including lung cancer. In this study, we show that CK2 is positively involved in Hh/Gli signaling in lung cancer cell lines A549 and H1299. First, we found a correlation between CK2α and Gli1 mRNA levels in 100 primary lung cancer tissues. Down-regulation of Gli1 expression and transcriptional activity were demonstrated after the silencing of CK2α in lung cancer cells. In addition, CK2α siRNA down-regulated the expression of Hh target genes. Furthermore, two small-molecule CK2α inhibitors led to a dose-dependent inhibition of Gli1 expression and transcriptional activity in lung cancer cells. Reversely, forced over-expression of CK2α resulted in an increase both in Gli1 expression and transcriptional activity in A549 cells. Finally, the inhibition of Hh/Gli by CK2α siRNA led to a reduction of a cancer stem cell-like side population that shows higher ABCG2 expression level. Thus, we report that the inhibition of CK2α down-regulates Hh/Gli signaling and subsequently reduces stem-like side population in human lung cancer cells.
authors: Thoracic Oncology Laboratory, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, United States of America.
authors: Shulin
authors: S
authors: Zhang
authors: Yucheng
authors: Y
authors: Wang
authors: Jian-Hua
authors: JH
authors: Mao
authors: David
authors: D
authors: Hsieh
authors: Il-Jin
authors: IJ
authors: Kim
authors: Li-Min
authors: LM
authors: Hu
authors: Zhidong
authors: Z
authors: Xu
authors: Hao
authors: H
authors: Long
authors: David M
authors: DM
authors: Jablons
authors: Liang
authors: L
authors: You
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000378:metabolism; D002452:Cell Count; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D059748:Proteolysis / Q000187:drug effects; D058985:Side-Population Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D054852:Small Molecule Libraries / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D000071676:Zinc Finger Protein GLI1
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C400551:GLI1 protein, human; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; C570325:CSNK2A1 protein, human; D047390:Casein Kinase II