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.
Highlights
Raf kinase inhibitor protein (RKIP), known as phosphatidylethanolamine-binding protein1 (PEBP1), is a highly conserved, small (23 kDa), cytosolic protein originally purified from bovine brain [1,2]
In what concerns the involvement of RKIP protein in the immuno-oncology topic, there is already some disperse information that strongly suggest a role for RKIP in the modulation of tumour microenvironment components, in controlling the infiltration of specific immune cells and secretion of pro-metastatic factors [44,45]
RKIP inversely correlated with the myeloid/lymphoid-ratio and was suppressed in patients suffering from chronic inflammatory disease, suggesting that RKIP may be indicative of a skewing of the (DC-vaccine-triggered) immune response towards chronic inflammation/myeloid immune suppression rather than towards an effective anti-tumour response [74]
Summary
Raf kinase inhibitor protein (RKIP), known as phosphatidylethanolamine-binding protein. This protein is widely expressed in normal human tissues, being recognized as having an important role in multiple physiological processes, such as spermatogenesis, neural development, cardiac output and membrane biosynthesis [2,3] This multifunctional capacity of RKIP is associated with its involvement in the modulation of several signalling pathways (Reviewed at [4,5,6,7,8]). In what concerns the involvement of RKIP protein in the immuno-oncology topic, there is already some disperse information that strongly suggest a role for RKIP in the modulation of tumour microenvironment components, in controlling the infiltration of specific immune cells and secretion of pro-metastatic factors [44,45]. RKIP function as an inflammatory and immune modulator and, we will discuss its implications in oncological diseases
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