Evidence map›Paper›PMID 37085490›Full record

ArticleCell death & disease2023

Downregulation of the Rho GTPase pathway abrogates resistance to ionizing radiation in wild-type p53 glioblastoma by suppressing DNA repair mechanisms.

Yuli Thamires Magalhaes, Viktor Kalbermatter Boell, Giovanna Duo Cardella, Fabio Luis Forti

RetractedOpen access · goldAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

18 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
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  7. The Role of RAS in CNS Tumors: A Key Player or an Overlooked Oncogene?International journal of molecular sciences · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Yuli Thamires Magalhaes *Laboratory of Biomolecular Systems Signaling, Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
Viktor Kalbermatter BoellLaboratory of Biomolecular Systems Signaling, Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
Giovanna Duo CardellaLaboratory of Biomolecular Systems Signaling, Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
Fabio Luis FortiLaboratory of Biomolecular Systems Signaling, Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil. flforti@iq.usp.br.ORCID http://orcid.org/0000-0002-2278-6396
Universidade de São Paulo · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma (GBM), the most common aggressive brain tumor, is characterized by rapid cellular infiltration and is routinely treated with ionizing radiation (IR), but therapeutic resistance inevitably recurs. The actin cytoskeleton of glioblastoma cells provides their high invasiveness, but it remains unclear whether Rho GTPases modulate DNA damage repair and therapeutic sensitivity. Here, we irradiated glioblastoma cells with different p53 status and explored the effects of Rho pathway inhibition to elucidate how actin cytoskeleton disruption affects the DNA damage response and repair pathways. p53-wild-type and p53-mutant cells were subjected to Rho GTPase pathway modulation by treatment with C3 toxin; knockdown of mDia-1, PFN1 and MYPT1; or treatment with F-actin polymerization inhibitors. Rho inhibition increased the sensitivity of glioma cells to IR by increasing the number of DNA double-strand breaks and delaying DNA repair by nonhomologous end-joining in p53-wild-type cells. p53 knockdown reversed this phenotype by reducing p21 expression and Rho signaling activity, whereas reactivation of p53 in p53-mutant cells by treatment with PRIMA-1 reversed these effects. The interdependence between p53 and Rho is based on nuclear p53 translocation facilitated by G-actin and enhanced by IR. Isolated IR-resistant p53-wild-type cells showed an altered morphology and increased stress fiber formation: inhibition of Rho or actin polymerization decreased cell viability in a p53-dependent manner and reversed the resistance phenotype. p53 silencing reversed the Rho inhibition-induced sensitization of IR-resistant cells. Rho inhibition also impaired the repair of IR-damaged DNA in 3D spheroid models. Rho GTPase activity and actin cytoskeleton dynamics are sensitive targets for the reversal of acquired resistance in GBM tumors with wild-type p53.

Indexed as

DNA RepairGlioblastomarho GTP-Binding ProteinsDNADown-RegulationHumansNeoplasm Recurrence, LocalProfilinsRadiation, IonizingTumor Suppressor Protein p53DNAPFN1 protein, humanProfilinsrho GTP-Binding ProteinsTumor Suppressor Protein p53

Identifiers

PMID37085490
PMCPMC10121706
OpenAlexW4366742995

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.