Evidence map›Paper›PMID 25925024›Full record

ArticleScientific reports2015

SMIFH2 has effects on Formins and p53 that perturb the cell cytoskeleton.

Tadamoto Isogai, Rob van der Kammen, Metello Innocenti

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

51 citing papers in PubMed, 81 citations in OpenAlex.

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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

3 authors at 2 institutions in 1 country.

Tadamoto IsogaiDivision of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Rob van der KammenDivision of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Metello InnocentiDivision of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
The Netherlands Cancer Institute · NLOncode Institute · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Formin proteins are key regulators of the cytoskeleton involved in developmental and homeostatic programs, and human disease. For these reasons, small molecules interfering with Formins' activity have gained increasing attention. Among them, small molecule inhibitor of Formin Homology 2 domains (SMIFH2) is often used as a pharmacological Formin blocker. Although SMIFH2 inhibits actin polymerization by Formins and affects the actin cytoskeleton, its cellular mechanism of action and target specificity remain unclear. Here we show that SMIFH2 induces remodelling of actin filaments, microtubules and the Golgi complex as a result of its effects on Formins and p53. We found that SMIFH2 triggers alternated depolymerization-repolymerization cycles of actin and tubulin, increases cell migration, causes scattering of the Golgi complex, and also cytotoxicity at high dose. Moreover, SMIFH2 reduces expression and activity of p53 through a post-transcriptional, proteasome-independent mechanism that influences remodelling of the cytoskeleton. As the action of SMIFH2 may go beyond Formin inhibition, only short-term and low-dose SMIFH2 treatments minimize confounding effects induced by loss of p53 and cytotoxicity.

Indexed as

Actin CytoskeletonActinsCell LineCell Line, TumorCell MovementGolgi ApparatusHCT116 CellsHEK293 CellsHumansMicrofilament ProteinsMicrotubulesProteasome Endopeptidase ComplexRNA Processing, Post-TranscriptionalSmall Molecule LibrariesThionesTubulinActinsMicrofilament ProteinsProteasome Endopeptidase ComplexSmall Molecule LibrariesSMIFH2 compoundThionesTP53 protein, humanTubulinTumor Suppressor Protein p53Uracil

Identifiers

PMID25925024
PMCPMC5386218
OpenAlexW2084408246

What OpenQuestion holds

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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.