Perspectives on signaling for biological- and processed food-related advanced glycation end-products and its role in cancer progression

Receptor for advanced glycation end-products (RAGE) is a multifunctional receptor binds a broad spectrum of ligands and mediates responses to cell damage and stress conditions. It also activates programs leading to acute and chronic inflammation and implicated in several pathological diseases, including cancer. In this review, we presented the non-enzymatic reaction of reducing sugar with the amino groups of proteins, lipids, and nucleic acids. This reaction initiates a complex series of rearrangements and dehydrations, and then produces a class of irreversibly cross-linked heterogeneous fluorescent moieties, termed advanced glycation end products (AGEs). There is a growing body of evidence that interaction of processes food-related AGEs with a cell surface receptor RAGE brings out the generation of oxidative stress and subsequently evokes proliferative, angiogenic and inflammatory reactions, thereby being involved in the development and progression of various types of cancers. This review is an insightful assessment of molecular mechanisms through which RAGE signaling contributes to the enhancement and survival of the tumorigenic cell. Here we summarize the procurement of individual ligands of RAGE like amphoterin, calcium-binding proteins, and resultant mediation of RAGE signaling pathway, which partially can elucidate the elevated risk of several cancers. Besides, we summarize many factors or conditions including APE1 (apurinic/apyrimidinic endonuclease 1), retinol mutations, retinoblastoma (Rb), proteinase 3 (PR3) hypoxia and so on through which RAGE signaling presents an establishment of cancerous environment. Additionally, we also reviewed some recent findings that give shreds of evidence for presenting the role of RAGE and its ligands in the advanced stage of cancers.