Understanding Mechanisms of RKIP Regulation to Improve the Development of New Diagnostic Tools

SIMPLE SUMMARY: Raf Kinase Inhibitor protein is a protein that governs multiple intracellular signalling involved primarily in the progression of tumours and the development of metastases. In this review, we discussed the main mechanisms that regulate the expression and activity of RKIP with the aim of identifying the link between the transcriptional, post-transcriptional and post-translational events in different tumour settings. We also tried to analyse the studies that have measured the levels of RKIP in biological fluids in order to highlight the possible advantages and potential of RKIP assessment to obtain an accurate diagnosis and prognosis of various tumours. ABSTRACT: One of the most dangerous aspects of cancer cell biology is their ability to grow, spread and form metastases in the main vital organs. The identification of dysregulated markers that drive intracellular signalling involved in the malignant transformation of neoplastic cells and the understanding of the mechanisms that regulate these processes is undoubtedly a key objective for the development of new and more targeted therapies. RAF-kinase inhibitor protein (RKIP) is an endogenous tumour suppressor protein that affects tumour cell survival, proliferation, and metastasis. RKIP might serve as an early tumour biomarker since it exhibits significantly different expression levels in various cancer histologies and it is often lost during metastatic progression. In this review, we discuss the specific impact of transcriptional, post-transcriptional and post-translational regulation of expression and activation/inhibition of RKIP and focus on those tumours for which experimental data on all these factors are available. In this way, we could select how these processes cooperate with RKIP expression in (1) Lung cancer; (2) Colon cancer, (3) Breast cancer; (4) myeloid neoplasm and Multiple Myeloma, (5) Melanoma and (6) clear cell Renal Cell Carcinoma. Furthermore, since RKIP seems to be a key marker of the development of several tumours and it may be assessed easily in various biological fluids, here we discuss the potential role of RKIP dosing in more accessible biological matrices other than tissues. Moreover, this objective may intercept the still unmet need to identify new and more accurate markers for the early diagnosis and prognosis of many tumours.