Hyper activation of β-catenin signalling induced by IKKε inhibition thwarts colorectal cancer cell proliferation

Cell Proliferation
Jie ChenJian Peng

Abstract

Aberrant activation of Wnt/β-catenin signalling contributes significantly to the development of human colorectal cancers and β-catenin is the key signalling molecule transducing canonical Wnt/β-catenin signalling. Therefore, β-catenin is a promising therapeutic target for cancer treatment. This study demonstrates that the oncogenic IKKε kinase phosphorylates β-catenin to restrain its hyper activation, therefore promoting colorectal cancer (CRC) cell proliferation. IKKε and β-catenin expression levels in human colorectal cancer tissues and cell lines were analysed by immunohistochemical staining and Western blotting. The regulation of IKKε on Wnt/β-catenin signalling pathway was studied by reporter assay and real-time PCR analysis in the context of IKKε stably knocking down. Co-immunoprecipitation was conducted to monitor the interaction between IKKε and β-catenin. Kinase assay was performed to measure β-catenin post-translational modifications induced by IKKε. Oncogenic IKKε kinase is required for the proliferation of colorectal cancer cells. Mechanistically, inhibition of IKKε results in β-catenin hyper activation and thwarts CRC cell proliferation. Furthermore, IKKε phosphorylates β-catenin and inhibits the activation of β-ca...Continue Reading

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Citations

Feb 2, 2018·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Qing LiHongzhi Sun
Nov 17, 2019·Cancer Medicine·Min YinJie Lu

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