The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity - PubMed (original) (raw)

. 2017 Aug 15;20(7):1692-1704.

doi: 10.1016/j.celrep.2017.07.055.

Shan Zhu 2, Xinxin Song 3, Xiaofang Sun 2, Yong Fan 2, Jinbao Liu 2, Meizuo Zhong 4, Hua Yuan 5, Lin Zhang 6, Timothy R Billiar 3, Michael T Lotze 3, Herbert J Zeh 3rd 3, Rui Kang 3, Guido Kroemer 7, Daolin Tang 8

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The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity

Yangchun Xie et al. Cell Rep. 2017.

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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.

Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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