RKIP as an inflammatory and immune system modulator: implications in cancer

Abstract

Raf kinase inhibitor protein (RKIP), an important modulator of intracellular signalling pathways, is commonly downregulated in multiple cancers. This reduction, or loss of expression, is correlated not only with the presence of metastasis, contributing to RKIP’s classification as a metastasis suppressor, but also with tumour aggressiveness and poor prognosis. Recent findings suggest a strong involvement of RKIP in the modulation of tumour microenvironment components, particularly by controlling the infiltration of specific immune cells and secretion of pro-metastatic factors. Additionally, RKIP interaction with multiple signalling molecules seems to potentiate its function as a regulator of inflammatory processes, mainly through stimulation of anti- or pro-inflammatory cytokines. Furthermore, RKIP is involved in the modulation of immunotherapeutic drugs response, through diverse mechanisms that sensitize cells to apoptosis. In the present review, we will provide updated information about the role of RKIP as an inflammatory and immune modulator and its potential implications in cancer will be addressed.