CK2-NCoR signaling cascade promotes prostate tumorigenesis
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Jung-Yoon Yoo1,*, Beom Jin Lim2,*, Hyo-Kyoung Choi1, Soon Won Hong2, Ho Sung Jang3, Changsoo Kim4, Kyung-Hee Chun1,5, Kyung-Chul Choi6, and Ho-Geun Yoon1
1 Department of Biochemistry and Molecular Biology, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Korea
2 Department of Pathology, Yonsei University College of Medicine, Seoul 120-752, Korea
3 Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea
4 Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
5 Genitourinary Cancer Branch, Division of Translational and Clinical Research II, National Cancer Center Research Institute and Hospital, Ilsandong-gu, Goyang-si, Gyeonggi-do, Korea
6 Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap-DONG, Songpa-gu, Seoul 138-736, Korea
* Contributed equally to the work
Kyung-Chul Choi, email:
Ho-Geun Yoon, email:
Keywords: CK2α, NCoR, Prostate cancer, IP-10, transcriptional regulation
Received: May 7, 2013, Accepted: May 10, 2013, Published: May 11, 2013
The aberrant expressions of casein kinase 2 (CK2) was found in prostate cancer patient and cell lines, but little is known of the detailed mechanisms implicated in prostate tumorigenesis. In this study, we report that both CK2 activity and CK2-mediated NCoR phosphorylation are significantly elevated in the androgen-independent prostate cancer cell line DU145 and PC-3 compared with RWPE1 and LNCaP cells. Increased phosphorylation inversely correlates with the mRNA level of the NCoR-regulated gene, interferon-γ-inducible protein 10 (IP-10). CK2 inhibition abrogated NCoR phosphorylation, IP-10 transcriptional repression, and the invasion activity of PC-3 cells. Inhibition of the CK2-NCoR network significantly reduced in vivo PC-3 cell tumorigenicity, likely due to transcriptional derepression of IP-10. Clinicopathological analyses revealed that increased CK2-mediated NCoR phosphorylation significantly correlates with poor survival among prostate cancer patients. These findings elucidate a CK2-modulated oncogenic cascade in prostate tumorigenesis.
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