Evidence map›Paper›PMID 35047450›Full record

ReviewJournal of cancer prevention2021

Double-edged Sword Role of Iron-loaded Ferritin in Extracellular Vesicles.

Shinya Toyokuni, Yingyi Kong, Hao Zheng, Danyang Mi, Misako Katabuchi, Yashiro Motooka, Fumiya Ito

Open access · diamondAbstract readReview
In one paragraph

Review in Journal of cancer prevention, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.5field-weighted citation impact, top 16% 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

10 citing papers in PubMed, 14 citations in OpenAlex.

  1. Ferroptosis and cancer: when iron turns against tumors.Cellular and molecular life sciences : CMLS · 2025
    Review
  2. Review
  3. Article
  4. Article
  5. Assessment of the Impact of Trace Essential Metals on Cancer Development.International journal of molecular sciences · 2024
    Review
  6. Article
  7. Environmental impact on carcinogenesis under BRCA1 haploinsufficiency.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2023
    Review
  8. Iron as spirit of life to share under monopoly.Journal of clinical biochemistry and nutrition · 2022
    Article
  9. Review
  10. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Shinya ToyokuniDepartment of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID https://orcid.org/0000-0002-5757-1109
Yingyi KongDepartment of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID https://orcid.org/0000-0002-6481-0745
Hao ZhengDepartment of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID https://orcid.org/0000-0002-2821-4153
Danyang MiDepartment of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID https://orcid.org/0000-0003-2035-0596
Misako KatabuchiDepartment of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID https://orcid.org/0000-0003-2998-6056
Yashiro MotookaDepartment of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID https://orcid.org/0000-0002-4230-7559
Fumiya ItoDepartment of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID https://orcid.org/0000-0001-5310-9630
Nagoya University · JPNagoya University Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human epidemiological and animal studies have demonstrated that excess iron is a risk for cancer. The responsible mechanisms are: 1) increased intracellular iron catalyzes the Fenton reaction to generate hydroxyl radicals, leading to mutagenic oxidative DNA lesions; 2) iron is necessary for cellular proliferation as cofactors of many enzymes. Thus, iron-excess milieu promotes selecting cellular evolution to ferroptosis-resistance, a major basis for carcinogenesis. Ferritin is a 24-subunit nanocage protein required for iron storage under the regulation of the iron-regulatory protein (IRP)/iron-responsive element (IRE) system. Ferritin is a serum marker, representing total body iron storage. However, how ferritin is secreted extracellularly has been unelucidated. We recently discovered that an exosomal marker CD63 is regulated by the IRP/IRE system and that iron-loaded ferritin is secreted as extracellular vesicles under the guidance of nuclear receptor coactivator 4 (NCOA4). On the other hand, we found that macrophages under asbestos-induced ferroptosis emit ferroptosis-dependent extracellular vesicles (FedEVs), which are received by nearby mesothelial cells, resulting in significant mutagenic DNA damage. Therefore, cells, including macrophages, can share excess iron with other cells, via iron-loaded ferritin packaged in extracellular vesicles as safe non-catalytic iron. However, similar process, such as one involving FedEVs, may cause accumulation of excess iron in other specific cells, which may eventually promote carcinogenesis.

Indexed as

AsbestosExtracellular vesiclesFerritinFerroptosisIron

Identifiers

PMID35047450
PMCPMC8749322
OpenAlexW4206612914

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.