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Oncogenic potential of CK 2α and its regulatory role in EGF ‐induced HDAC 2 expression in human liver cancer
Author(s) -
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.
Publication year - 2014
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12652
Subject(s) - cancer research , ectopic expression , protein kinase b , gene knockdown , cell cycle , carcinogenesis , histone deacetylase , biology , cancer cell , cancer , cell growth , signal transduction , histone , apoptosis , cell culture , microbiology and biotechnology , biochemistry , gene , genetics
Histone deacetylase 2 ( HDAC 2) 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 HDAC 2 remains unknown. In this study, we show that expression of CK 2α (casein kinase II α subunit) was up‐regulated in a large cohort of human HCC patients, and that high expression of CK 2α was significantly associated with poor prognosis of HCC patients in terms of five‐year overall survival. It was also found that CK 2α over‐expression positively correlated with HDAC 2 over‐expression in a subset of HCC s. We observed that treatment with epidermal growth factor ( EGF ) elicited an increase in CK 2α expression and Akt phosphorylation, causing induction of HDAC 2 expression in liver cancer cells. It was also observed that ectopic expression of dominant‐negative CK 2α blocked EGF ‐induced HDAC 2 expression, and that ectopic CK 2α expression attenuated the suppressive effect of Akt knockdown on HDAC 2 expression in liver cancer cells. Targeted disruption of CK 2α influenced the cell cycle, causing a significant increase in the number of liver cancer cells remaining in G 2 /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 CK 2α in liver tumorigenesis. Furthermore, a regulatory mechanism for HDAC 2 expression is proposed whereby EGF induces transcriptional activation of HDAC 2 by CK 2α/Akt activation in liver cancer cells. Therefore, this makes CK 2α a promising target in cancer therapy.