Casein Kinase 2 Interacting Protein-1 Suppresses Glioma Cell Proliferation via Regulating the AKT/GSK3 β / β -Catenin Pathway

• Published in: BioMed research international 2019-01, Vol.2019 (2019), p.1-11
• Main Authors: Cheng, Shi-Xiang, Zhang, Wen-Bin, Shao, Xue-Fei, Yi, Tai-Long, Zhu, Lei, Jin, Jing-Yun, Ren, Deng-Peng, Xi, Yan-Guo, Sun, Sheng-Kai
• Format: Article
• Language: English
• Subjects: Adult; AKT protein; Apoptosis; beta Catenin - metabolism; Biomedical research; Biotechnology; Brain cancer; Cancer therapies; Casein; Casein kinase II; Cell adhesion & migration; Cell cycle; Cell growth; Cell Line, Tumor; Cell Proliferation; Cholecystokinin; Cloning; Cytoskeleton; DNA biosynthesis; Female; Flow cytometry; Fluorescence; Gene Expression Regulation, Neoplastic; Glioma; Glioma - metabolism; Glioma - mortality; Glioma - pathology; Glioma cells; Glycogen Synthase Kinase 3 beta - metabolism; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins - biosynthesis; Kinases; Male; Middle Aged; Phosphorylation; Physiology; Protein expression; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Rank tests; Signal Transduction; Therapeutic applications; Tumorigenesis; Tumors; Western blotting; β-Catenin
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2019/5653212

Objective. Casein kinase 2 interacting protein-1 (CKIP-1) has exhibited multiple functions in regulating cell proliferation, apoptosis, differentiation, and cytoskeleton. CKIP-1 also plays an important role as a critical regulator in tumorigenesis. The aim of this study is to further examine the function of CKIP-1 in glioma cells. Methods. The expression level of CKIP-1 protein was determined in gliomas tissues and cell lines by immunohistochemistry stain and western blotting while the association of CKIP-1 expression with prognosis was analyzed by Kaplan-Meier method and compared by log-rank test. CKIP-1 was overexpressed or silenced in gliomas cell lines. CCK-8, colony formation assay, and BrdU incorporation assay were used to determine cell proliferation and DNA synthesis. Cell cycle and apoptosis rate were determined with fluorescence-activated cell sorting (FACS) method. Then, expression of key members in AKT/GSK3β/β-catenin pathway was detected by western blot analysis. Results. In the present study, we reported new evidence that CKIP-1 was reversely associated with the proliferation of glioma cells and survival in glioma patients. Additionally, the overexpressed CKIP-1 significantly inhibited glioma cell proliferation. Further experiments revealed that CKIP-1 functioned through its antiproliferative and proapoptotic activity in glioma cells. Importantly, mechanistic investigations suggested that CKIP-1 sharply suppressed the activity of AKT by inhibiting the phosphorylation, markedly downregulated the phosphorylated GSK3β at Ser9, and promoted β-catenin degradation. Conclusions. Overall, our results provided new insights into the clinical significance and molecular mechanism of CKIP-1 in glioma, which indicated CKIP1 might function as a therapeutic target for clinical treatment of glioma.