Evidence map›Paper›PMID 26464464›Full record

ArticleJournal of the National Cancer Institute2016

Reactivation of p53 by a Cytoskeletal Sensor to Control the Balance Between DNA Damage and Tumor Dissemination.

Cecilia Herraiz, Fernando Calvo, Pahini Pandya, Gaia Cantelli, Irene Rodriguez-Hernandez, Jose L Orgaz, NaRa Kang, Tinghine Chu, Erik Sahai, Victoria Sanz-Moreno

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

Article in Journal of the National Cancer Institute, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
10.3field-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

37 citing papers in PubMed, 178 citations in OpenAlex.

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  8. Amoeboid migration in health and disease: Immune responsesFrontiers in cell and developmental biology · 2022
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  13. First-in-Human Study of AT13148, a Dual ROCK-AKT Inhibitor in Patients with Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Article
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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

10 authors at 3 institutions in 2 countries.

Cecilia HerraizTumor Plasticity Laboratory, Randall Division of Cell and Molecular Biophysics, King's College London, London, UK (CH, PP, GC, IRH, JLO, NK, TC, VSM); Tumor Cell Biology Laboratory, Cancer Research UK London Research Institute, London, UK (FC, ES).Current affiliations: Tumor Microenvironment Team, Institute of Cancer Research, Chester Beatty Laboratories, London, UK (FC); Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia and IMIB-Arrixaca, Murcia, Spain (CH).
Fernando CalvoTumor Plasticity Laboratory, Randall Division of Cell and Molecular Biophysics, King's College London, London, UK (CH, PP, GC, IRH, JLO, NK, TC, VSM); Tumor Cell Biology Laboratory, Cancer Research UK London Research Institute, London, UK (FC, ES).Current affiliations: Tumor Microenvironment Team, Institute of Cancer Research, Chester Beatty Laboratories, London, UK (FC); Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia and IMIB-Arrixaca, Murcia, Spain (CH).
Pahini PandyaTumor Plasticity Laboratory, Randall Division of Cell and Molecular Biophysics, King's College London, London, UK (CH, PP, GC, IRH, JLO, NK, TC, VSM); Tumor Cell Biology Laboratory, Cancer Research UK London Research Institute, London, UK (FC, ES).Current affiliations: Tumor Microenvironment Team, Institute of Cancer Research, Chester Beatty Laboratories, London, UK (FC); Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia and IMIB-Arrixaca, Murcia, Spain (CH).
Gaia CantelliTumor Plasticity Laboratory, Randall Division of Cell and Molecular Biophysics, King's College London, London, UK (CH, PP, GC, IRH, JLO, NK, TC, VSM); Tumor Cell Biology Laboratory, Cancer Research UK London Research Institute, London, UK (FC, ES).Current affiliations: Tumor Microenvironment Team, Institute of Cancer Research, Chester Beatty Laboratories, London, UK (FC); Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia and IMIB-Arrixaca, Murcia, Spain (CH).
Irene Rodriguez-HernandezTumor Plasticity Laboratory, Randall Division of Cell and Molecular Biophysics, King's College London, London, UK (CH, PP, GC, IRH, JLO, NK, TC, VSM); Tumor Cell Biology Laboratory, Cancer Research UK London Research Institute, London, UK (FC, ES).Current affiliations: Tumor Microenvironment Team, Institute of Cancer Research, Chester Beatty Laboratories, London, UK (FC); Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia and IMIB-Arrixaca, Murcia, Spain (CH).
Jose L OrgazTumor Plasticity Laboratory, Randall Division of Cell and Molecular Biophysics, King's College London, London, UK (CH, PP, GC, IRH, JLO, NK, TC, VSM); Tumor Cell Biology Laboratory, Cancer Research UK London Research Institute, London, UK (FC, ES).Current affiliations: Tumor Microenvironment Team, Institute of Cancer Research, Chester Beatty Laboratories, London, UK (FC); Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia and IMIB-Arrixaca, Murcia, Spain (CH).
NaRa KangTumor Plasticity Laboratory, Randall Division of Cell and Molecular Biophysics, King's College London, London, UK (CH, PP, GC, IRH, JLO, NK, TC, VSM); Tumor Cell Biology Laboratory, Cancer Research UK London Research Institute, London, UK (FC, ES).Current affiliations: Tumor Microenvironment Team, Institute of Cancer Research, Chester Beatty Laboratories, London, UK (FC); Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia and IMIB-Arrixaca, Murcia, Spain (CH).
Tinghine ChuTumor Plasticity Laboratory, Randall Division of Cell and Molecular Biophysics, King's College London, London, UK (CH, PP, GC, IRH, JLO, NK, TC, VSM); Tumor Cell Biology Laboratory, Cancer Research UK London Research Institute, London, UK (FC, ES).Current affiliations: Tumor Microenvironment Team, Institute of Cancer Research, Chester Beatty Laboratories, London, UK (FC); Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia and IMIB-Arrixaca, Murcia, Spain (CH).
Erik SahaiTumor Plasticity Laboratory, Randall Division of Cell and Molecular Biophysics, King's College London, London, UK (CH, PP, GC, IRH, JLO, NK, TC, VSM); Tumor Cell Biology Laboratory, Cancer Research UK London Research Institute, London, UK (FC, ES).Current affiliations: Tumor Microenvironment Team, Institute of Cancer Research, Chester Beatty Laboratories, London, UK (FC); Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia and IMIB-Arrixaca, Murcia, Spain (CH).
Victoria Sanz-MorenoTumor Plasticity Laboratory, Randall Division of Cell and Molecular Biophysics, King's College London, London, UK (CH, PP, GC, IRH, JLO, NK, TC, VSM); Tumor Cell Biology Laboratory, Cancer Research UK London Research Institute, London, UK (FC, ES).Current affiliations: Tumor Microenvironment Team, Institute of Cancer Research, Chester Beatty Laboratories, London, UK (FC); Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia and IMIB-Arrixaca, Murcia, Spain (CH). victoria.sanz_moreno@kcl.ac.uk.
Institute of Cancer Research · GBUniversidad de Murcia · ESKing's College London · GB

Funding

Cancer Research UK 12065Cancer Research UK 15154Cancer Research UK C33043/A12065Medical Research Council C97993HWorldwide Cancer Research 15-0273
6 · The paper itself

Abstract

backgroundAbnormal cell migration and invasion underlie metastasis, and actomyosin contractility is a key regulator of tumor invasion. The links between cancer migratory behavior and DNA damage are poorly understood.

methodsUsing 3D collagen systems to recapitulate melanoma extracellular matrix, we analyzed the relationship between the actomyosin cytoskeleton of migrating cells and DNA damage. We used multiple melanoma cell lines and microarray analysis to study changes in gene expression and in vivo intravital imaging (n = 7 mice per condition) to understand how DNA damage impacts invasive behavior. We used Protein Tissue Microarrays (n = 164 melanomas) and patient databases (n = 354 melanoma samples) to investigate the associations between markers of DNA damage and actomyosin cytoskeletal features. Data were analyzed with Student's and multiple t tests, Mann-Whitney's test, one-way analysis of variance, and Pearson correlation. All statistical tests were two-sided.

resultsMelanoma cells with low levels of Rho-ROCK-driven actomyosin are subjected to oxidative stress-dependent DNA damage and ATM-mediated p53 protein stabilization. This results in a specific transcriptional signature enriched in DNA damage/oxidative stress responsive genes, including Tumor Protein p53 Inducible Protein 3 (TP53I3 or PIG3). PIG3, which functions in DNA damage repair, uses an unexpected catalytic mechanism to suppress Rho-ROCK activity and impair tumor invasion in vivo. This regulation was suppressed by antioxidants. Furthermore, PIG3 levels decreased while ROCK1/2 levels increased in human metastatic melanomas (ROCK1 vs PIG3; r = -0.2261, P < .0001; ROCK2 vs PIG3: r = -0.1381, P = .0093).

conclusionsThe results suggest using Rho-kinase inhibitors to reactivate the p53-PIG3 axis as a novel therapeutic strategy; we suggest that the use of antioxidants in melanoma should be very carefully evaluated.

Indexed as

ActomyosinDNA DamageDNA RepairAnimalsCell Line, TumorCytoskeletonGene Expression Regulation, NeoplasticHumansImmunohistochemistryIntracellular Signaling Peptides and ProteinsMelanomaMiceMicroscopy, ConfocalMicroscopy, FluorescenceOxidative StressProtein Array AnalysisActomyosinIntracellular Signaling Peptides and ProteinsProto-Oncogene ProteinsReactive Oxygen Speciesrho-Associated KinasesROCK1 protein, humanROCK2 protein, humanTP53I3 protein, humanTumor Suppressor Protein p53

Identifiers

PMID26464464
PMCPMC4712681
OpenAlexW2179828787

What OpenQuestion holds

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LicenceCC BY
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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.