Necroptosis has been shown to play important roles in various pathophysiological conditions, including ischemic injuries,9, 17, 18, 19 inflammatory diseases20 and neurodegeneration.21, 22 RIP3 is emerging as a key molecule in the regulation of necroptosis.1, 10, 11 Interestingly, most cancer cells display a defect in RIP3, thereby obtaining the ability to evade necroptosis.26 In the current study, we demonstrate the roles of transcript factor Sp1 and epigenetic regulator in the regulation of RIP3 expression in cancer cells (Figure 7). Here, SP1 is linked to cancer.