@article{98e15c81fc704436ab8eae58489b0af4,
title = "The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity",
abstract = "Ferroptosis is a form of regulated cell death that may facilitate the selective elimination of tumor cells. The tumor suppressor p53 (TP53) has been demonstrated to promote ferroptosis via a transcription-dependent mechanism. Here, we show that TP53 limits erastin-induced ferroptosis by blocking dipeptidyl-peptidase-4 (DPP4) activity in a transcription-independent manner. Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results in ferroptosis. These findings reveal a direct molecular link between TP53 and DPP4 in the control of lipid metabolism and may provide a precision medicine strategy for the treatment of colorectal cancer by induction of ferroptosis.",
keywords = "ACSL4, NOX, NRF2, SLC7A11, TP53, ddp4, ferroptosis, iron, lipid peroxidation, precision medicine",
author = "Yangchun Xie and Shan Zhu and Xinxin Song and Xiaofang Sun and Yong Fan and Jinbao Liu and Meizuo Zhong and Hua Yuan and Lin Zhang and Billiar, {Timothy R.} and Lotze, {Michael T.} and Zeh, {Herbert J.} and Rui Kang and Guido Kroemer and Daolin Tang",
note = "Funding Information: We thank Christine Heiner (Department of Surgery, University of Pittsburgh) for her critical reading of the manuscript. This work was supported by grants from the US NIH ( R01GM115366 , R01CA160417 , and R01CA181450 ), the Natural Science Foundation of Guangdong Province ( 2016A030308011 ), the American Cancer Society (research scholar grant RSG-16-014-01-CDD ), the National Natural Science Foundation of China ( 31671435 , 81400132 , and 8177100253 ), the National Funds of Developing Local Colleges and Universities Grant ( B16056001 ), a Frontier and Key Technology Innovation Special Grant from the Department of Science and Technology of Guangdong Province ( 2016B030229008 ), and the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2017). This project partly utilized University of Pittsburgh Cancer Institute shared resources supported by award P30CA047904 . G.K. is supported by the Ligue contre le Cancer ({\'e}quipe labelis{\'e}e); Agence National de la Recherche (ANR) Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases ; Association pour la recherche sur le cancer (ARC) ; Canc{\'e}rop{\^o}le Ile-de-France ; Institut National du Cancer (INCa) ; Institut Universitaire de France ; Fondation pour la Recherche M{\'e}dicale (FRM) ; the European Commission (ArtForce) ; the European Research Council (ERC) ; the LeDucq Foundation ; the LabEx Immuno-Oncology ; the RHU Torino Lumi{\`e}re ; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE) ; the SIRIC Cancer Research and Personalized Medicine (CARPEM) ; and the Paris Alliance of Cancer Research Institutes (PACRI) . Publisher Copyright: {\textcopyright} 2017 The Author(s)",
year = "2017",
month = aug,
day = "15",
doi = "10.1016/j.celrep.2017.07.055",
language = "English",
volume = "20",
pages = "1692--1704",
journal = "Cell Reports",
issn = "2211-1247",
number = "7",
}