Conclusion
Our study suggests that IKKε is a potential target to combat CRC induced by aberrant Wnt/β-catenin signalling.
Methods
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.
Objective
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. Materials and
Results
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-catenin signalling.