Abstract 219: PHF20 induced necrotic like cell death mediated by ROS via enhanced mitochondrial biogenesis

The importance of PHD finger protein 20 (PHF20) in the cellular process is recently emerging as a regulator for the p53 and NF-kB signaling as well as the reprograming process of induced pluripotent stem cell. In this study, we have provided the clear evidence that PHF20 exhibit the novel function in tumorigenesis by regulating the mitochondria biogenesis. Overexpression of PHF20 increases mitochondria biogenesis via up-regulation of peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1-α) in HCT116 cells. PHF20 overexpression enhances mitochondrial respiratory capacity and oxygen consumption, leading to the accumulation of reactive oxygen species (ROS). Accumulated ROS by PHF20 causes the necrotic like cell death in HCT116 cells. The measurement of mitochondrial ROS in the cells expressing PHF20 revealed that excessive production of mitochondrial ROS facilitates the formation of mitochondrial permeability transition pore, resulting in the loss of mitochondrial membrane potential. PHF20-mediated ROS accumulation damages DNA and leads to over-activation of PARP but not caspase. Antioxidants and PARP-1 inhibitor are able to rescue PHF20 induced cell death, whereas z-VAD, pan-caspase inhibitor, had no effects. Immunohistochemical analysis of various human cancer revealed that PHF20 expression is highly elevated in most of tumor compared to normal tissue. Taken together, PHF20 appears to be tumor-specific antigen and PHF20-mediated PGC1-α upregulation is responsible for the elevation of intracellular ROS generation, resulting the necrotic like cell death. Thus, this study provided the new concept for treating glioma patients and novel pharmacological target in various cancers including glioblastoma and hepatocellular carcinoma Citation Format: Jisoo Park, Yuwen Li, Gyeyeong Kong, Kisun Mun, Hyunji Lee, Dohoon Kim, Quangdon Tran, Ming Wang, Bingjie Peng, Youngeun Hong, Gang Min Hur, Jongsun Park. PHF20 induced necrotic like cell death mediated by ROS via enhanced mitochondrial biogenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 219.