Abstract
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.
Highlights
Casein kinase 2 (CK2) is a multifunctional protein kinase with a wide range of protein substrates, many of which are critically involved in the processes of cell cycle control, cellular differentiation, proliferation, and metabolism [1]
It is noteworthy that the levels of Nuclear receptor corepressor (NCoR) and NCoR phosphorylation is elevated in LNCaP-derivative C4-2B cells compared with LNCaP cells, to a less than both DU145 and PC-3 cells, implying the plausible role of www.impactjournals.com/oncotarget
We suggest a possible molecular mechanism by which NCoR modulates the invasive growth of androgen independent prostate cancer cells in a casein kinase 2 (CK2)-dependent manner
Summary
Casein kinase 2 (CK2) is a multifunctional protein kinase with a wide range of protein substrates, many of which are critically involved in the processes of cell cycle control, cellular differentiation, proliferation, and metabolism [1]. Overexpression of CK2α leads to increased c-myc expression in T cell lymphoma [7], NFκB activation in NIH3T3 cells [8], and protects PC-3 cells from etoposideinduced apoptosis [9]. CK2α overexpression cooperates with c-myc or p53 loss (or mutation) at the lpr locus to promote tumorigenesis [11]. Transgenic expression of CK2α under the MMTV promoter resulted in late onset squamous adenocarcinomas with increased c-myc and β-catenin expression [12]. CK2 participates in the control of Snail, a major factor for epithelial-mesenchymal transition, by stabilizing and positively regulating Snail repressive function and its interaction with the mSin3A corepressor [13]. CK2 is recently highlighted as promising target for cancer therapies [5, 14, 15]
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