Evidence map›Paper›PMID 24583638›Full record

ArticleCell death and differentiation2014

Oncogene-induced reactive oxygen species fuel hyperproliferation and DNA damage response activation.

M Ogrunc, R Di Micco, M Liontos, L Bombardelli, M Mione, M Fumagalli, V G Gorgoulis, F d'Adda di Fagagna

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
186citing papers in PubMed, 1 pooled it
10.8field-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

186 citing papers in PubMed, 1 synthesis or guideline pooled it, 314 citations in OpenAlex.

  1. Pooled it
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  4. Review
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  9. Mitochondrial regulation of cellular senescence heterogeneity.Frontiers in cell and developmental biology · 2026
    Review
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  18. Exploring the oncogenic impact of heteroplasmicMitochondrial communications · 2025
    Article
  19. Review
  20. Article

126 more citing papers are in PubMed but not listed here.

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

8 authors at 2 institutions in 3 countries.

M OgruncIFOM Foundation, The FIRC Institute of Molecular Oncology Foundation, via Adamello 16, Milan, Italy.
R Di MiccoIFOM Foundation, The FIRC Institute of Molecular Oncology Foundation, via Adamello 16, Milan, Italy.
M LiontosMolecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, 75 Mikras Asias Street, Goudi, 11527 Athens, Greece.
L BombardelliIFOM Foundation, The FIRC Institute of Molecular Oncology Foundation, via Adamello 16, Milan, Italy.ORCID 0000000302132747
M MioneIFOM Foundation, The FIRC Institute of Molecular Oncology Foundation, via Adamello 16, Milan, Italy.
M FumagalliIFOM Foundation, The FIRC Institute of Molecular Oncology Foundation, via Adamello 16, Milan, Italy.
V G Gorgoulis1] Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, 75 Mikras Asias Street, Goudi, 11527 Athens, Greece [2] Basic Science II Center, Biomedical Research Foundation of the Academy of Athens, 4 Soranou Ephessiou Street, 11527 Athens, Greece.
F d'Adda di Fagagna1] IFOM Foundation, The FIRC Institute of Molecular Oncology Foundation, via Adamello 16, Milan, Italy [2] Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, Pavia, Italy.
IFOM · ITNational and Kapodistrian University of Athens · GR

Funding

European Research Council 322726Telethon GGP12059
6 · The paper itself

Abstract

Oncogene-induced reactive oxygen species (ROS) have been proposed to be signaling molecules that mediate proliferative cues. However, ROS may also cause DNA damage and proliferative arrest. How these apparently opposite roles can be reconciled, especially in the context of oncogene-induced cellular senescence, which is associated both with aberrant mitogenic signaling and DNA damage response (DDR)-mediated arrest, is unclear. Here, we show that ROS are indeed mitogenic signaling molecules that fuel oncogene-driven aberrant cell proliferation. However, by their very same ability to mediate cell hyperproliferation, ROS eventually cause DDR activation. We also show that oncogenic Ras-induced ROS are produced in a Rac1 and NADPH oxidase (Nox4)-dependent manner. In addition, we show that Ras-induced ROS can be detected and modulated in a living transparent animal: the zebrafish. Finally, in cancer we show that Nox4 is increased in both human tumors and a mouse model of pancreatic cancer and specific Nox4 small-molecule inhibitors act synergistically with existing chemotherapic agents.

Indexed as

Oxidative StressAnimalsCell Line, TumorCell ProliferationDNA DamageHumansMiceNADPH Oxidase 4NADPH OxidasesOxidation-ReductionPancreatic Neoplasmsrac1 GTP-Binding ProteinReactive Oxygen SpeciesXenograft Model Antitumor AssaysNADPH Oxidase 4NADPH OxidasesNOX4 protein, humanrac1 GTP-Binding ProteinRAC1 protein, humanReactive Oxygen Species

Identifiers

PMID24583638
PMCPMC4013514
OpenAlexW2171565634

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.