Regulation of Tumor Progression by Programmed Necrosis

Figure 4

Snail and Dlx-2 regulate metabolic stress-induced necrosis in tumors by inducing EMT, mitochondrial dysregulation, and oncogenic metabolism. GD-induced Snail and Dlx-2 may cause mitochondrial dysfunction, facilitating ROS production in response to GD. Increased ROS can induce insoluble protein aggregates containing p53, caspase, and beclin and cause necrosis through triggering the plasma membrane rupture and HMGB1 release. In addition, metabolic stress-induced necrosis is driven by increased ROS, which is stimulated by Snail and Dlx-2, which mediates EMT for tumor invasion in the absence of metabolic stress. The Dlx-2/GLS1/glutamine metabolic axis can regulate TGF-β/Wnt-induced, Snail-dependent EMT, and glycolytic switch. Metabolic stress-induced Snail and Dlx-2 expression contributes to tumor progression by promoting necrosis as well as by inducing EMT and oncogenic metabolism.