title: CK2α phosphorylates DBC1 and is involved in the progression of gastric carcinoma and predicts poor survival of gastric carcinoma patients.
abstract: CK2α 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 CK2α 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 CK2α and DBC1 in gastric carcinomas. Positive expression of CK2α and phospho-DBC1 predicted shorter overall survival and relapse-free survival by univariate analysis. Especially, CK2α expression was an independent prognostic indicator for gastric carcinoma patients. In gastric carcinoma cells, CK2α was bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2α was evidenced by co-immunoprecipitation of CK2α and DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. Inhibition of both CK2α 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 CK2α 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 CK2α and DBC1 inhibited the proliferation and invasive potential of gastric cancer cells. Therefore, our study suggests that CK2α-DBC1 pathway might be a new therapeutic target for the treatment of gastric carcinoma.
authors: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors: Jun Sang
authors: JS
authors: Bae
authors: See-Hyoung
authors: SH
authors: Park
authors: Kyoung Min
authors: KM
authors: Kim
authors: Keun Sang
authors: KS
authors: Kwon
authors: Chan Young
authors: CY
authors: Kim
authors: Hun Ku
authors: HK
authors: Lee
authors: Byung-Hyun
authors: BH
authors: Park
authors: Ho Sung
authors: HS
authors: Park
authors: Ho
authors: H
authors: Lee
authors: Woo Sung
authors: WS
authors: Moon
authors: Myoung Ja
authors: MJ
authors: Chung
authors: Karl G
authors: KG
authors: Sylvester
authors: Kyu Yun
authors: KY
authors: Jang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D047390:Casein Kinase II / Q000502:physiology*; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C527450:CCAR2 protein, human; D047390:Casein Kinase II
keywords: CK2; DBC1; carcinoma; phosphorylation; stomach