Casein Kinase 2 Interacting Protein-1 Suppresses Glioma Cell Proliferation via Regulating the AKTGSK3 β β -Catenin Pathway

Abstract EN

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.