Oncogenic potential of CK2[alpha] and its regulatory role in EGF-induced HDAC2 expression in human liver cancer

• Published in: The FEBS journal 2014-02, Vol.281 (3), p.851
• Main Authors: Kim, Hyung S, Chang, Young G, Bae, Hyun J, Eun, Jung W, Shen, Qingyu, Park, Se J, Shin, Woo C, Lee, Eun K, Park, Soha, Ahn, Young M, Park, Won S, Lee, Jung Y, Nam, Suk W
• Format: Article
• Language: English
• Subjects: Chemotherapy; Epidermal growth factor; Liver cancer; Pharmacology
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.12652

Histone deacetylase 2 (HDAC2) is aberrantly regulated and plays a pivotal role in the development of hepatocellular carcinoma (HCC) through regulation of cell-cycle components at the transcriptional level, but the underlying mechanism leading to oncogenic HDAC2 remains unknown. In this study, we show that expression of CK2[alpha] (casein kinase II [alpha] subunit) was up-regulated in a large cohort of human HCC patients, and that high expression of CK2[alpha] was significantly associated with poor prognosis of HCC patients in terms of five-year overall survival. It was also found that CK2[alpha] over-expression positively correlated with HDAC2 over-expression in a subset of HCCs. We observed that treatment with epidermal growth factor (EGF) elicited an increase in CK2[alpha] expression and Akt phosphorylation, causing induction of HDAC2 expression in liver cancer cells. It was also observed that ectopic expression of dominant-negative CK2[alpha] blocked EGF-induced HDAC2 expression, and that ectopic CK2[alpha] expression attenuated the suppressive effect of Akt knockdown on HDAC2 expression in liver cancer cells. Targeted disruption of CK2[alpha] influenced the cell cycle, causing a significant increase in the number of liver cancer cells remaining in G2/M phase, and suppressed growth via repression of Cdc25c and cyclin B in liver cancer cells. Taken together, our findings suggest the oncogenic potential of CK2[alpha] in liver tumorigenesis. Furthermore, a regulatory mechanism for HDAC2 expression is proposed whereby EGF induces transcriptional activation of HDAC2 by CK2[alpha]/Akt activation in liver cancer cells. Therefore, this makes CK2[alpha] a promising target in cancer therapy. [PUBLICATION ABSTRACT]