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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters / metabolism
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Carcinoma, Non-Small-Cell Lung / genetics
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Carcinoma, Non-Small-Cell Lung / pathology
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Casein Kinase II / antagonists & inhibitors
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Casein Kinase II / metabolism
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Cell Count
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Cell Line, Tumor
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Down-Regulation / drug effects
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Down-Regulation / genetics*
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Knockdown Techniques
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Gene Silencing / drug effects
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Humans
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Lung Neoplasms / genetics*
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Lung Neoplasms / pathology*
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Neoplasm Proteins / metabolism
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Neoplastic Stem Cells / drug effects
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Neoplastic Stem Cells / metabolism
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Neoplastic Stem Cells / pathology*
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Protein Kinase Inhibitors / pharmacology
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Proteolysis / drug effects
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Side-Population Cells / drug effects
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Side-Population Cells / metabolism
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Side-Population Cells / pathology
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Signal Transduction* / genetics
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Small Molecule Libraries / pharmacology
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic / drug effects
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Transcriptional Activation / drug effects
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Transcriptional Activation / genetics
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Up-Regulation / drug effects
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Up-Regulation / genetics
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Zinc Finger Protein GLI1
Substances
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ABCG2 protein, human
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters
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GLI1 protein, human
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Neoplasm Proteins
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Protein Kinase Inhibitors
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Small Molecule Libraries
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Transcription Factors
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Zinc Finger Protein GLI1
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CSNK2A1 protein, human
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Casein Kinase II