Evaluating the CRP Interactome: Insights into Possible Novel Roles in Cellular Signaling and Tumorigenicity

C-reactive protein (CRP) is a well-known acute phase reactant and putative biomarker for advancing and chronically established inflammation. Its biological activity across its multiple isoforms plays various roles in the initiation, potentiation, and resolution of inflammation. Its molecular signaling within the tissue microenvironment regulates cell–cell communication across cell types (e.g., epithelial cells, endothelial cells, fibroblasts, adipocytes, and immune cells) and affects the development of conditions such as cancer that are subject, at least in part, to inflammatory signaling. Considering the dynamic nature of CRP in modulating disease progression, and the growing evidence of the context-dependent direct molecular activity of CRP on regulating intra- and inter-cellular signaling, it is critical to further understand how this integral molecule alters cell signaling pathways. Although the ability of CRP to directly interact with some extracellular matrix proteins involved with inflammation and disease has been reported as early as the mid-1980s, recent advances in unbiased proteomics have revealed a broader interactome of protein–protein interactions (PPIs) involving CRP. The present study evaluates the CRP PPIs identified to date and explores the potential novel regulatory capacity of CRP on multiple key cellular functions in metabolism and cell–cell signaling, offering an updated framework of the possible biological activities of CRP relevant to tumorigenic processes.