Evidence map›Paper›PMID 25799988›Full record

ArticleNature2015

Ferroptosis as a p53-mediated activity during tumour suppression.

Le Jiang, Ning Kon, Tongyuan Li, Shang-Jui Wang, Tao Su, Hanina Hibshoosh, Richard Baer, Wei Gu

Open access · greenAbstract read
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2,076 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2,076citing papers in PubMed, 4 pooled it
40.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2,076 citing papers in PubMed, 4 syntheses or guidelines pooled it, 3,277 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Interaction of HIF-1a with various cell death pathways in tumor immune microenvironment (TIME).Apoptosis : an international journal on programmed cell death · 2026
    Pooled it
  4. Pooled it
  5. Ferroptosis in heatstroke: Mechanisms and therapeutic perspectives (Review).International journal of molecular medicine · 2026
    Review
  6. Review
  7. Ferroptosis in health and disease.Molecular biomedicine · 2026
    Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  18. Review
  19. Review
  20. Article

2,016 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Le JiangInstitute for Cancer Genetics, College of Physicians &Surgeons, Columbia University 1130 St Nicholas Ave, New York, New York 10032, USA.
Ning KonInstitute for Cancer Genetics, College of Physicians &Surgeons, Columbia University 1130 St Nicholas Ave, New York, New York 10032, USA.
Tongyuan LiInstitute for Cancer Genetics, College of Physicians &Surgeons, Columbia University 1130 St Nicholas Ave, New York, New York 10032, USA.
Shang-Jui WangInstitute for Cancer Genetics, College of Physicians &Surgeons, Columbia University 1130 St Nicholas Ave, New York, New York 10032, USA.
Tao Su1] Department of Pathology and Cell Biology, College of Physicians &Surgeons, Columbia University 630 West 168th Street, New York, New York 10032, USA [2] Herbert Irving Comprehensive Cancer Center, College of Physicians &Surgeons, Columbia University 1130 St Nicholas Ave, New York, New York 10032, USA.
Hanina Hibshoosh1] Department of Pathology and Cell Biology, College of Physicians &Surgeons, Columbia University 630 West 168th Street, New York, New York 10032, USA [2] Herbert Irving Comprehensive Cancer Center, College of Physicians &Surgeons, Columbia University 1130 St Nicholas Ave, New York, New York 10032, USA.
Richard Baer1] Institute for Cancer Genetics, College of Physicians &Surgeons, Columbia University 1130 St Nicholas Ave, New York, New York 10032, USA [2] Department of Pathology and Cell Biology, College of Physicians &Surgeons, Columbia University 630 West 168th Street, New York, New York 10032, USA [3] Herbert Irving Comprehensive Cancer Center, College of Physicians &Surgeons, Columbia University 1130 St Nicholas Ave, New York, New York 10032, USA.
Wei Gu1] Institute for Cancer Genetics, College of Physicians &Surgeons, Columbia University 1130 St Nicholas Ave, New York, New York 10032, USA [2] Department of Pathology and Cell Biology, College of Physicians &Surgeons, Columbia University 630 West 168th Street, New York, New York 10032, USA [3] Herbert Irving Comprehensive Cancer Center, College of Physicians &Surgeons, Columbia University 1130 St Nicholas Ave, New York, New York 10032, USA.
Columbia University · USCancer Genetics (United States) · US

Funding

PW1--A mediator of cell survival by NFKB and cell death by p53P01CA080058 · NCI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI AARONSON, STUART A · 2000 to 2016
$20.2M
The role of PTEN in basal-like breast cancerP01CA097403 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PARSONS, RAMON E · 2003 to 2013
$18.2M
CELL, MOLECULAR AND DEVELOPMENTAL BIOLOGY OF CANCERT32CA009503 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI GAUTIER, JEAN · 1985 to 2016
$6.8M
Regulation of p53 acetylation and deacetylation in tumorigenesis.R01CA085533 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GU, WEI · 2000 to 2021
$5.2M
The BARD1 tumor suppressor and breast cancerR01CA172272 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BAER, RICHARD J · 2013 to 2017
$1.7M
Mechanisms of novel cancer targets in ARF-mediated tumor suppressionR01CA169246 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GU, WEI · 2012 to 2016
$1.6M
Role of p53-mediated unconventional functions in tumor suppressionR01CA172023 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GU, WEI · 2012 to 2016
$1.6M
Regulation of Mdmx stability and subcellular localization by ubiquitinationR01CA166294 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GU, WEI · 2012 to 2016
$1.5M
NCI NIH HHS 2P01CA080058NCI NIH HHS 2P01CA097403NCI NIH HHS 5R01CA166294NCI NIH HHS 5R01CA169246NCI NIH HHS 5R01CA172023NCI NIH HHS P01 CA080058NCI NIH HHS P01 CA097403NCI NIH HHS R01 CA085533NCI NIH HHS R01 CA166294NCI NIH HHS R01 CA169246NCI NIH HHS R01 CA172023NCI NIH HHS R01 CA172272NCI NIH HHS T32 CA009503NCI NIH HHS T32-CA09503
6 · The paper itself

Abstract

Although p53-mediated cell-cycle arrest, senescence and apoptosis serve as critical barriers to cancer development, emerging evidence suggests that the metabolic activities of p53 are also important. Here we show that p53 inhibits cystine uptake and sensitizes cells to ferroptosis, a non-apoptotic form of cell death, by repressing expression of SLC7A11, a key component of the cystine/glutamate antiporter. Notably, p53(3KR), an acetylation-defective mutant that fails to induce cell-cycle arrest, senescence and apoptosis, fully retains the ability to regulate SLC7A11 expression and induce ferroptosis upon reactive oxygen species (ROS)-induced stress. Analysis of mutant mice shows that these non-canonical p53 activities contribute to embryonic development and the lethality associated with loss of Mdm2. Moreover, SLC7A11 is highly expressed in human tumours, and its overexpression inhibits ROS-induced ferroptosis and abrogates p53(3KR)-mediated tumour growth suppression in xenograft models. Our findings uncover a new mode of tumour suppression based on p53 regulation of cystine metabolism, ROS responses and ferroptosis.

Indexed as

Amino Acid Transport System y+AnimalsBiological TransportCell DeathCystineEmbryo, MammalianEmbryonic DevelopmentHumansIronMiceNeoplasmsOxidative StressProto-Oncogene Proteins c-mdm2Reactive Oxygen SpeciesSubstrate SpecificityTumor Suppressor Protein p53Amino Acid Transport System y+CystineIronMdm2 protein, mouseProto-Oncogene Proteins c-mdm2Reactive Oxygen SpeciesSLC7A11 protein, humanTumor Suppressor Protein p53

Identifiers

PMID25799988
PMCPMC4455927
OpenAlexW2067107606

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.