Evidence map›Paper›PMID 27746021›Full record

ArticleMolecular cell2016

Direct Regulation of Alternative Splicing by SMAD3 through PCBP1 Is Essential to the Tumor-Promoting Role of TGF-β.

Veenu Tripathi, Katherine M Sixt, Shaojian Gao, Xuan Xu, Jing Huang, Roberto Weigert, Ming Zhou, Ying E Zhang

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

50 citing papers in PubMed, 101 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Veenu TripathiLaboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Katherine M SixtLaboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Shaojian GaoGenetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Xuan XuLaboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Jing HuangLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Roberto WeigertLaboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Ming ZhouLaboratory of Protein Characterization, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Ying E ZhangLaboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: zhangyin@mail.nih.gov.
National Cancer Institute · USLeidos (United States) · US

Funding

Molecular Mechanisms of TGF-beta Signaling PathwayZIABC010419 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ZHANG, YING E · 2009 to 2025
$14.9M
Intramural NIH HHS ZIA BC010419
6 · The paper itself

Abstract

In advanced stages of cancers, TGF-β promotes tumor progression in conjunction with inputs from receptor tyrosine kinase pathways. However, mechanisms that underpin the signaling cooperation and convert TGF-β from a potent growth inhibitor to a tumor promoter are not fully understood. We report here that TGF-β directly regulates alternative splicing of cancer stem cell marker CD44 through a phosphorylated T179 of SMAD3-mediated interaction with RNA-binding protein PCBP1. We show that TGF-β and EGF respectively induce SMAD3 and PCBP1 to colocalize in SC35-positive nuclear speckles, and the two proteins interact in the variable exon region of CD44 pre-mRNA to inhibit spliceosome assembly in favor of expressing the mesenchymal isoform CD44s over the epithelial isoform CD44E. We further show that the SMAD3-mediated alternative splicing is essential to the tumor-promoting role of TGF-β and has a global influence on protein products of genes instrumental to epithelial-to-mesenchymal transition and metastasis.

Indexed as

Gene Expression Regulation, NeoplasticAlternative SplicingAnimalsCell Line, TumorDNA-Binding ProteinsEpidermal Growth FactorEpithelial-Mesenchymal TransitionExonsFemaleGene Expression ProfilingHeterogeneous-Nuclear RibonucleoproteinsHumansHyaluronan ReceptorsLung NeoplasmsMiceMice, NudeCD44 protein, humanDNA-Binding ProteinsEpidermal Growth FactorHeterogeneous-Nuclear RibonucleoproteinsHyaluronan ReceptorsPCBP1 protein, humanProtein IsoformsRNA-Binding ProteinsRNA PrecursorsSmad3 ProteinSMAD3 protein, humanThreonineTransforming Growth Factor betaalternative splicingCD44EMTmetastasisPCBP1SMAD3TGF-β

Identifiers

PMID27746021
PMCPMC5123764
OpenAlexW2529957804

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.