Evidence map›Paper›PMID 23435423›Full record

ArticleOncogene2014

The RNA-binding protein Rbfox2: an essential regulator of EMT-driven alternative splicing and a mediator of cellular invasion.

C Braeutigam, L Rago, A Rolke, L Waldmeier, G Christofori, J Winter

Abstract read
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In one paragraph

Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

109 citing papers in PubMed, 172 citations in OpenAlex.

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49 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

6 authors at 3 institutions in 2 countries.

C BraeutigamDepartment of Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
L RagoDepartment of Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
A RolkeDepartment of Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
L WaldmeierDepartment of Biomedicine, University of Basel, Basel, Switzerland.
G ChristoforiDepartment of Biomedicine, University of Basel, Basel, Switzerland.
J Winter1] Department of Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany [2] Institute of Human Genetics, University Medical Center of the Johannes Gutenberg, University of Mainz, Mainz, Germany.
Max Planck Institute of Immunobiology and Epigenetics · DEUniversity of Basel · CHUniversity Medical Center of the Johannes Gutenberg University Mainz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The epithelial-mesenchymal transition (EMT), a prerequisite for cancer progression and metastasis formation, is regulated not only at the transcriptional but also at the post-transcriptional level, including at the level of alternative pre-mRNA splicing. Several recent studies have highlighted the involvement of splicing factors, including epithelial splicing regulatory proteins (Esrps) and RNA-binding Fox protein 2 (Rbfox2), in this process. Esrps regulate epithelial-specific splicing, and their expression is downregulated during EMT. By contrast, the role of Rbfox2 is controversial because Rbfox2 regulates epithelial as well as mesenchymal splicing events. Here, we have used several established cell culture models to investigate the functions of Rbfox2 during EMT. We demonstrate that induction of an EMT upregulates the expression of Rbfox2, which correlates with an increase in Rbfox2-regulated splicing events in the cortactin (Cttn), Pard3 and dynamin 2 (Dnm2) transcripts. At the same time, however, the epithelial-specific ability to splice the Enah, Slk and Tsc2 transcripts is either reduced or lost completely by Rbfox2, which might be due, in part, to downregulation of the expression of the Esrps cooperative factors. Depletion of Rbfox2 during EMT did not prevent the activation of transforming growth factor-β signaling, the upregulation of mesenchymal markers or changes in cell morphology toward a mesenchymal phenotype. In addition, this depletion did not influence cell migration. However, depletion of Rbfox2 in cells that have completed an EMT significantly reduced their invasive potential. Taken together, our results suggest that during an EMT, Rbfox2-regulated splicing shifts from epithelial-to mesenchymal-specific events, leading to a higher degree of tissue invasiveness.

Indexed as

AnimalsCell Line, TumorCell MovementDown-RegulationEpithelial CellsEpithelial-Mesenchymal TransitionMiceNeoplasm InvasivenessRNA-Binding ProteinsRNA SplicingRNA Splicing FactorsUp-RegulationRbfox2 protein, mouseRNA-Binding ProteinsRNA Splicing Factors

Identifiers

PMID23435423
OpenAlexW2063213431

What OpenQuestion holds

Textmetadata
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.