Cited by 540Ferroptosis and cancer prognosisCancer-related Molecular PathwaysCell death mechanisms and regulation

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p53 in ferroptosis regulation: the new weapon for the old guardian

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Liu, Yanqing, Gu, Wei·2022·Cell Death & Differentiation

DOI 10.1038/s41418-022-00943-yPMC PMC9091200

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Abstract

Although the conventional activities of p53 such as cell cycle arrest, senescence, and apoptosis are well accepted as the major checkpoints in stress responses, accumulating evidence implicates the importance of other tumor suppression mechanisms. Among these unconventional activities, an iron-dependent form of non-apoptotic cell death, termed ferroptosis, attracts great interest. Unlike apoptotic cell death, activation of p53 alone is not sufficient to induce ferroptosis directly; instead, through its metabolic targets, p53 is able to modulate the ferroptosis response in the presence of ferroptosis inducers such as GPX4 inhibitors or high levels of ROS. Here, we review the role of ferroptosis in p53-mediated tumor suppression, with a focus on what cellular factors are critical for p53-dependent ferroptosis during tumor suppression and how p53 modulates both the canonical (GPX4-dependent) and the non-canonical (GPX4-independent) ferroptosis pathways. We also discuss the possibility of targeting p53-mediated ferroptotic responses for the treatment of human cancers and potentially, other diseases.

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1 retracted

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Authors: Liu, Y., & Gu, W.
Affiliations: Herbert Irving Comprehensive Cancer Center (US)
Corresponding author: Gu, Wei
ORCID: Liu, Yanqing
Gu, Wei
Venue: Cell Death & Differentiation
Publisher: Springer Science and Business Media LLC
Published: 2022-01-27
Volume: 29
Issue: 5
Pages: 895-910
ISSN: 1350-9047 (ISSN-L)
1476-5403
DOI: 10.1038/s41418-022-00943-y
PMC: PMC9091200
OpenAlex: W4210576858
Cited by: 540
References: 141
Citations by year: 2026: 88 · 2025: 153 · 2024: 128 · 2023: 110 · 2022: 60
FWCI: 19.51
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Cell Death and Differentiation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Health & Human Services | NIH | National Cancer Institute (R35CA253059, R01CA254970)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: p53, ferroptosis, tumor suppression, GPX4, iron metabolism, reactive oxygen species, non-apoptotic cell death, cancer therapy
MeSH terms: Ferroptosis, Humans, Neoplasms, Tumor Suppressor Protein p53, Apoptosis, Reactive Oxygen Species

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p53 in ferroptosis regulation: the new weapon for the old guardian

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