Protein kinase CK2α is overexpressed in colorectal cancer and modulates cell proliferation and invasion via regulating EMT-related genes

Background: Protein kinase CK2 is a highly conserved, ubiquitous protein serine/threonine kinase that phosphorylates many substrates and has a global role in numerous biological and pathological processes. Overexpression of the protein kinase CK2 alpha subunit (CK2 alpha) has been associated with the malignant transformation of several tissues, with not nearly as much focus on the role of CK2 alpha in colorectal cancer (CRC). The aims of this study are to investigate the function and regulatory mechanism of CK2 alpha in CRC development. Methods: Expression levels of CK2 alpha were analyzed in 144 patients (104 with CRC and 40 with colorectal adenoma) by immunohistochemistry. Proliferation, senescence, motility and invasion assays as well as immunofluorescence staining and western blots were performed to assess the effect of CK2 alpha in CRC. Results: The immunohistochemical expression of nuclear CK2 alpha was stronger in tumor tissues than in adenomas and normal colorectal tissues. Suppression of CK2 alpha by small-interfering RNA or the CK2 alpha activity inhibitor emodin inhibited proliferation of CRC cells, caused G0/G1 phase arrest, induced cell senescence, elevated the expression of p53/p21 and decreased the expression of C-myc. We also found that knockdown of CK2 alpha suppressed cell motility and invasion. Significantly, CK2 alpha inhibition resulted in beta-catenin transactivation, decreased the expression levels of vimentin and the transcription factors snail1 and smad2/3, and increased the expression of E-cadherin, suggesting that CK2 alpha regulates the epithelial-mesenchymal transition (EMT) process in cancer cells. Conclusions: Our results indicate that CK2 alpha plays an essential role in the development of CRC, and inhibition of CK2 alpha may serve as a promising therapeutic strategy for human CRC.