Based on these observations we propose a model in which continuous production of mediators such as, ROS-, TGF-β, and IL-6 at smoldering inflammatory sites (due to chronic infection, tissue injury, or tumor growth) aberrantly upregulate TG2 expression, which then orchestrates multiple downstream signals to affect such critical processes as EMT and acquisition of stem cell like (CSC) characteristics in epithelial cells. Here, TGFB1 is linked to neoplasm.