AGE-RAGE synergy influences programmed cell death signaling to promote cancer

Advanced glycation end products (AGEs) are formed as a result of non-enzymatic reaction between the free reducing sugars and proteins, lipids, or nucleic acids. AGEs are predominantly synthesized during chronic hyperglycemic conditions or aging. AGEs interact with their receptor RAGE and activate various sets of genes and proteins of the signal transduction pathway. Accumulation of AGEs and upregulated expression of RAGE is associated with various pathological conditions including diabetes, cardiovascular diseases, neurodegenerative disorders, and cancer. The role of AGE-RAGE signaling has been demonstrated in the progression of various types of cancer and other pathological disorders. The expression of RAGE increases manifold during cancer progression. The activation of AGE-RAGE signaling also perturbs the cellular redox balance and modulates various cell death pathways. The programmed cell death signaling often altered during the progression of malignancies. The cellular reprogramming of AGE-RAGE signaling with cell death machinery during tumorigenesis is interesting to understand the complex signaling mechanism of cancer cells. The present review focus on multiple molecular paradigms relevant to cell death particularly Apoptosis, Autophagy, and Necroptosis that are considerably influenced by the AGE-RAGE signaling in the cancer cells. Furthermore, the review also attempts to shed light on the provenience of AGE-RAGE signaling on oxidative stress and consequences of cell survival mechanism of cancer cells.