KNOCKDOWN OF CASEIN KINASE le INHIBITS CELL PROLIFERATION AND INVASION OF COLORECTAL CANCER CELLS VIA INHIBITION OF THE Wnt/β-CATENIN SIGNALING

Deregulation of casein kinase 1 epsilon (CK1 epsilon) is involved in the development of multiple pathological disorders such as cancer, however the function and molecular mechanism of CK1 epsilon in cancer are still unclear. In the present study, we aimed to investigate the role of CK1 epsilon in human colorectal cancer (CRC). The expression of CK1 epsilon was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was performed to observe the effects of lentivirus-mediated CK1 epsilon shRNA (Lv-shCK1 epsilon) on cell proliferation and invasive potential by MTT and Transwell assays in CRC cell line (SW480). As a result, we found that the expression of CK1 epsilon protein was significantly increased in CRC tissues compared with that in adjacent non-cancerous tissues (ANCT) (68.9% vs 42.2%, P=0.017), and was correlated with the Duke's staging and depth of invasion in CRC patients (P=0.012; P=0.015). Knockdown of CK1 epsilon reduced cell proliferation and invasion of CRC cells followed by the downregulation of wnt3 alpha, beta-catenin, PCNA and MMP-9. In conclusion, our findings show that high expression of CK1 epsilon is positively associated with the Duke's staging and depth of invasion in CRC patients, and knockdown of CK1 epsilon suppresses the growth and invasion of CRC cells through inhibition of the wnt/beta-catenin signaling, suggesting that CK1 epsilon may serve as a promising therapeutic target for the treatment of CRC.