Cell Reports (Aug 2017)
The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity
- 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, III,
- Rui Kang,
- Guido Kroemer,
- Daolin Tang
Affiliations
- Yangchun Xie
- The Third Affiliated Hospital, Center for DAMP Biology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Protein Modification and Degradation Laboratory, Guangzhou Medical University, Guangzhou, Guangdong 510510, China
- Shan Zhu
- The Third Affiliated Hospital, Center for DAMP Biology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Protein Modification and Degradation Laboratory, Guangzhou Medical University, Guangzhou, Guangdong 510510, China
- Xinxin Song
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Xiaofang Sun
- The Third Affiliated Hospital, Center for DAMP Biology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Protein Modification and Degradation Laboratory, Guangzhou Medical University, Guangzhou, Guangdong 510510, China
- Yong Fan
- The Third Affiliated Hospital, Center for DAMP Biology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Protein Modification and Degradation Laboratory, Guangzhou Medical University, Guangzhou, Guangdong 510510, China
- Jinbao Liu
- The Third Affiliated Hospital, Center for DAMP Biology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Protein Modification and Degradation Laboratory, Guangzhou Medical University, Guangzhou, Guangdong 510510, China
- Meizuo Zhong
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Hua Yuan
- School of Nursing, Jilin University, Changchun, Jilin 130021, China
- Lin Zhang
- Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Timothy R. Billiar
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Michael T. Lotze
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Herbert J. Zeh, III
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Rui Kang
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Guido Kroemer
- Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France
- Daolin Tang
- The Third Affiliated Hospital, Center for DAMP Biology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Protein Modification and Degradation Laboratory, Guangzhou Medical University, Guangzhou, Guangdong 510510, China
- DOI
- https://doi.org/10.1016/j.celrep.2017.07.055
- Journal volume & issue
-
Vol. 20,
no. 7
pp. 1692 – 1704
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
