CK2alpha phosphorylates DBC1 and is involved in the progression of gastric carcinoma and predicts poor survival of gastric carcinoma patients.
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Bae JS, Park SH, Kim KM, Kwon KS, Kim CY, Lee HK, Park BH, Park HS, Lee H, Moon WS, Chung MJ, Sylvester KG, Jang KY
CK2alpha phosphorylates DBC1 and is involved in the progression of gastric carcinoma and predicts poor survival of gastric carcinoma patients.
Int J Cancer. 2015 Feb 15;136(4):797-809. doi: 10.1002/ijc.29043. Epub 2014 Jul 1.
- PubMed ID
- 24962073 [ View in PubMed]
- Abstract
CK2alpha has diverse effects on the tumorigenesis owing to its kinase activity, which phosphorylates various proteins involved in tumorigenesis. We, therefore, investigated the expression and role of CK2alpha in the phosphorylation of deleted in breast cancer 1 (DBC1) in gastric carcinomas. We used 187 gastric carcinomas and human gastric cancer cells to investigate the roles and relationship between CK2alpha and DBC1 in gastric carcinomas. Positive expression of CK2alpha and phospho-DBC1 predicted shorter overall survival and relapse-free survival by univariate analysis. Especially, CK2alpha expression was an independent prognostic indicator for gastric carcinoma patients. In gastric carcinoma cells, CK2alpha was bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2alpha was evidenced by co-immunoprecipitation of CK2alpha and DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. Inhibition of both CK2alpha and DBC1 decreased proliferation and invasive activity of cancer cells. Decreased migration and invasive activity was associated with a downregulation of MMP2, MMP9 and the epithelial-mesenchymal transition. A mutation at the phosphorylation site of DBC1 also downregulated the signals related with the epithelial-mesenchymal transition. Our study demonstrated that CK2alpha is an independent prognostic indicator for gastric carcinoma patients and is involved in tumorigenesis by regulating the phosphorylation of DBC1. In addition, the blocking of CK2alpha and DBC1 inhibited the proliferation and invasive potential of gastric cancer cells. Therefore, our study suggests that CK2alpha-DBC1 pathway might be a new therapeutic target for the treatment of gastric carcinoma.