Effect of Raf kinase inhibitor protein expression on malignant biological behavior and progression of colorectal cancer

The Raf kinase inhibitor protein (RKIP) is a novel metastasis suppressor. RKIP was previously found to have low expression in a colorectal cancer (CRC) patient cohort by immunohistochemistry. However, the role of RKIP in CRC remains undetermined. In the present study, immunohistochemistry was performed to compare RKIP expression between 129 paired stage II CRC and adjacent non-tumorous tissues. The correlations between clinical parameters, prognosis and RKIP expression were evaluated. To investigate the effect of RKIP on proliferation and metastasis, RKIP was overexpressed and knocked down in colon cancer cell lines. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell and wound-healing assays were performed. Murine models were established to confirm the influence of RKIP on malignant tumor phenotypes in vivo. Our results showed that RKIP expression was significantly decreased in the CRC tissues compared to the adjacent non-cancerous tissues (p<0.001) and was correlated with the risk of relapse in stage II CRC (p<0.05). Overexpression of RKIP suppressed HCT116 cell metastasis in vitro and in vivo, whereas knockdown of RKIP expression in SW480 cells and its murine model increased metastatic ability (p<0.05). No effect of RKIP on cell proliferation in CRC was observed. These data suggest that RKIP is an important metastasis-suppressor gene in CRC. The re-expression of RKIP could be a potential therapeutic target for antimetastatic strategies for CRC.