Abstract

CK2a 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 CK2a 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 CK2a and DBC1 in gastric carcinomas. Positive expression of CK2a and phospho-DBC1 predicted shorter overall survival and relapse-free survival by univariate analysis. Especially, CK2a expression was an independent prognostic indicator for gastric carcinoma patients. In gastric carcinoma cells, CK2a was bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2a was evidenced by co-immunoprecipitation of CK2a and DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. Inhibition of both CK2a 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 CK2a 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 CK2a and DBC1 inhibited the proliferation and invasive potential of gastric cancer cells. Therefore, our study suggests that CK2a-DBC1 pathway might be a new therapeutic target for the treatment of gastric carcinoma.

View details for DOI 10.1002/ijc.29043

View details for Web of Science ID 000346089900027

View details for PubMedID 24962073