Hyper activation of β‐catenin signalling induced by IKK ε inhibition thwarts colorectal cancer cell proliferation

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 IKK ε kinase phosphorylates β‐catenin to restrain its hyper activation, therefore promoting colorectal cancer ( CRC ) cell proliferation. Materials and methods IKK ε and β‐catenin expression levels in human colorectal cancer tissues and cell lines were analysed by immunohistochemical staining and Western blotting. The regulation of IKK ε on Wnt/β‐catenin signalling pathway was studied by reporter assay and real‐time PCR analysis in the context of IKK ε stably knocking down. Co‐immunoprecipitation was conducted to monitor the interaction between IKK ε and β‐catenin. Kinase assay was performed to measure β‐catenin post‐translational modifications induced by IKK ε. Results Oncogenic IKK ε kinase is required for the proliferation of colorectal cancer cells. Mechanistically, inhibition of IKK ε results in β‐catenin hyper activation and thwarts CRC cell proliferation. Furthermore, IKK ε phosphorylates β‐catenin and inhibits the activation of β‐catenin signalling. Conclusion Our study suggests that IKK ε is a potential target to combat CRC induced by aberrant Wnt/β‐catenin signalling.