Changes in Expression of Tumor Suppressor Gene RKIP Impact How Cancers Interact with Their Complex Environment

SIMPLE SUMMARY: Raf Kinase Inhibitor Protein (RKIP) is a known metastasis suppressor that has regulatory effects on several different pathways. The reduced expression of this protein is strongly correlated with poor prognosis in many cancer types, and several of the cell-specific consequences of its loss have been determined. The tumor microenvironment is the intricate and ever-changing network of extracellular matrix, immune cells, blood and lymphatic vessels, fibroblasts, and signaling molecules that surrounds the tumor. The tumor can facilitate changes to the microenvironment, and the state of the microenvironment can be promotive or restrictive towards tumor growth and metastasis. Loss of RKIP expression has known promotive effects on tumor metastasis and expression of proteins that are able to influence the tumor microenvironment in cancer cells. In this review, we aim to collect and aggregate the relevant research regarding RKIP’s effects on the tumor microenvironment. ABSTRACT: Tumor microenvironment (TME) is the immediate environment where cancer cells reside in a tumor. It is composed of multiple cell types and extracellular matrix. Microenvironments can be restrictive or conducive to the progression of cancer cells. Initially, microenvironments are suppressive in nature. Stepwise accumulation of mutations in oncogenes and tumor suppressor genes enables cancer cells to acquire the ability to reshape the microenvironment to advance their growth and metastasis. Among the many genetic events, the loss-of-function mutations in tumor suppressor genes play a pivotal role. In this review, we will discuss the changes in TME and the ramifications on metastasis upon altered expression of tumor metastasis suppressor gene RKIP in breast cancer cells.