The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity

• DOI: 10.1016/j.celrep.2017.07.055
• Publication Date: 2017-08-15T16:16:49Z
• Authors: Yangchun Xie; Shan Zhu; Xinxin Song; Xiaofang Sun; Yong Fan; Jinbao Liu; Meizuo Zhong; Hua Yuan; Lin Zhang; Timothy R. Billiar; Michael T. Lotze; Herbert J. Zeh; Rui Kang; Guido Kroemer; Daolin Tang
• Keywords: Transcription

Ferroptosis is a form of regulated cell death that may facilitate the selective elimination tumor cells. The suppressor p53 (TP53) has been demonstrated to promote ferroptosis via transcription-dependent mechanism. Here, we show TP53 limits erastin-induced by blocking dipeptidyl-peptidase-4 (DPP4) activity in transcription-independent manner. Loss prevents nuclear accumulation DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results ferroptosis. These findings reveal direct molecular link between control metabolism provide precision medicine strategy for treatment colorectal cancer induction