Raf-kinase inhibitor protein (RKIP): A therapeutic target in colon cancer

Raf-kinase inhibitor protein (RKIP) plays a significant role in maintaining cell homeostasis, and its downregulation is a hallmark of various cancers, including colorectal cancer (CRC). It modulates several signals, including MAPK (Raf/MEK/ERK), NF-κB, STAT3, cell cycle, and GPCR signaling by modulating phosphorylation state. It's binding to Raf-1 inhibits phosphorylation and makes the signaling molecules inactive. In the case of NF-κB, which plays a central role in drug resistance, RKIP interacts with IκBα and inhibits IKKα, IKKβ, and NIK by preventing their phosphorylation, thereby maintaining NF-κB in an inactive state. A reduction in the expression level of RKIP increases the metastasis and promotes the signaling associated with cancer progression. This review examines the role of RKIP in the aggressiveness and metastasis of CRC. Several signal pathways influenced by changes in the expression level of RKIP are discussed in detail. Strategies like the use of inhibitors, understanding the role of miRNA, immunotherapy, and combined therapies have been discussed in detail, along with the clinical implications of RKIP in CRC.