A Negative Regulatory Role for RKIP in Breast Cancer Immune Response.

Abstract

Simple SummaryBreast cancer is the second most common cancer in women worldwide. Regulation of breast cancer metastasis remains an elusive phenomenon. Elucidating the mechanistic pathway of metastatic signaling may identify targets for regulating cancer metastatic potential. Raf-1 kinase inhibitor protein (RKIP) has been shown to negatively regulate signaling pathways involved in cancer progression and metastasis. RKIP may suppress metastasis of breast cancer cells by downregulating elements of the immune system. Raf-1 kinase inhibitor protein was first identified as a negative regulator of the Raf signaling pathway. Subsequently, it was shown to have a causal role in containing cancer progression and metastasis. Early studies suggested that RKIP blocks cancer progression by inhibiting the Raf-1 pathway. However, it is not clear if the RKIP tumor and metastasis suppression function involve other targets. In addition to the Raf signaling pathway, RKIP has been found to modulate several other signaling pathways, affecting diverse biological functions including immune response. Recent advances in medicine have identified both positive and negative roles of immune response in cancer initiation, progression and metastasis. It is possible that one way that RKIP exerts its effect on cancer is by targeting an immune response mechanism. Here, we provide evidence supporting the causal role of tumor and metastasis suppressor RKIP in downregulating signaling pathways involved with immune response in breast cancer cells and discuss its potential ramification on cancer therapy.