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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2018 | Research

CDK5RAP3 suppresses Wnt/β-catenin signaling by inhibiting AKT phosphorylation in gastric cancer

Authors: Chao-Hui Zheng, Jia-Bin Wang, Man-Qiang Lin, Peng-Yang Zhang, Li-Chao Liu, Jian-Xian Lin, Jun Lu, Qi-Yue Chen, Long-Long Cao, Mi Lin, Ru-Hong Tu, Jian-Wei Xie, Ping Li, Chang-Ming Huang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

Abstract

Background

CDK5RAP3 was initially isolated as a binding protein of the CDK5 activator p35. Although CDK5RAP3 has been shown to negatively regulate the Wnt/β-catenin signaling pathway in gastric cancer by repressing GSK-3β phosphorylation, its in-depth mechanism has not been determined.

Methods

Following CDK5RAP3 overexpression or knock down, CDK5RAP3 signaling pathways were investigated in gastric cancer cells by Western Blotting. Cell growth, invasion and migration were also evaluated in gastric cancer cell lines. We analyzed CDK5RAP3, AKT, p-AKT (Ser473), GSK-3β and p-GSK-3β (Ser9) expression in gastric tumor samples and adjacent non-tumor tissues from 295 patients using immunohistochemistry and Western Blotting. The prognostic significance of CDK5RAP3 and p-AKT (Ser473) was confirmed by a Log-rank test.

Results

Our study demonstrated that the expression of p-AKT (Ser473) and p-GSK-3β (Ser9) was negatively correlated with CDK5RAP3 in stable gastric cancer cell lines. CDK5RAP3 repressed AKT phosphorylation, which promoted GSK-3β phosphorylation, thereby suppressing β-catenin protein expression and, consequently, gastric cancer. The protein level of CDK5RAP3 was markedly decreased in most gastric tumor tissues compared with adjacent non-tumor tissues, and the levels of p-AKT (Ser473) and p-GSK-3β (Ser9) were also negatively correlated with those of CDK5RAP3. The prognostic value of CDK5RAP3 for overall survival was found to be dependent on AKT phosphorylation.

Conclusion

Our results demonstrated that CDK5RAP3 negatively regulates the Wnt/β-catenin signaling pathway by repressing AKT phosphorylation, which leads to better survival of patients with gastric cancer.

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Title: CDK5RAP3 suppresses Wnt/β-catenin signaling by inhibiting AKT phosphorylation in gastric cancer
Authors: Chao-Hui Zheng
Jia-Bin Wang
Man-Qiang Lin
Peng-Yang Zhang
Li-Chao Liu
Jian-Xian Lin
Jun Lu
Qi-Yue Chen
Long-Long Cao
Mi Lin
Ru-Hong Tu
Jian-Wei Xie
Ping Li
Chang-Ming Huang
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-018-0716-4

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Abstract

Background

Methods

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