Effects of RKIP loss in human and in animal models of colorectal cancer

Raf kinase inhibitor protein (RKIP) has been shown to be differentially regulated in a number of different human cancers. Typically, RKIP levels are found to be lower in tumor tissue than in normal tissue, and lower still in tumor metastases. In colorectal cancer (CRC), this is also the case; however interestingly in this disease, it has also been shown that the level of RKIP in the primary tumor correlates inversely with both the likelihood of metastatic relapse and with prognosis. Although this relationship with prognosis has clear clinical relevance, there is also some evidence that RKIP may provide even greater utility by acting as a predictive marker. In this review, we describe the evidence demonstrating the clear role for RKIP as a prognostic marker in CRC and go on to describe some of our evidence indicating a possible predictive role. Because there is as yet no mechanistic understanding of how low levels of RKIP affect prognosis in CRC, we have been using the RKIP knockout mouse to attempt to address this question. Here, we describe the current literature relating to the RKIP knockout mouse and our approach to using it to study the role of RKIP in CRC.