Ca2+/calmodulin-dependent protein kinase II regulates colon cancer proliferation and migration via ERK1/2 and p38 pathways.

ABSTRACT

AIM: To investigate the role of calmodulin-dependent protein kinase II (CaMKII) in colon cancer growth, migration and invasion. METHODS: CaMKII expression in colon cancer and paracancerous tissues was evaluated via immunochemistry. Transcriptional and posttranscriptional levels of CaMKIIin tissue samples and MMP2, MMP9 and TIMP-1 expression in the human colon cancer cell line HCT116 were assessed by qRT-PCR and western blot. Cell proliferation was detected with the MTT assay. Cancer cell migration and invasion were investigated with the Transwell culture system and wound-healing assay. RESULTS: We first demonstrated that CaMKII was over-expressed in human colon cancers and was associated with cancer differentiation. In the human colon cancer cell line HCT116, the CaMKII-specific inhibitor KN93, but not its inactive analogue KN92, decreased cancer cell proliferation. Furthermore, KN93 also significantly prohibited HCT116 cell migration and invasion. The specific inhibition of ERK1/2 or p38 decreased the proliferation and migration of colon cancer cells. CONCLUSION: Our findings highlight CaMKII as a potential critical mediator in human colon tumor development and metastasis.