Evidence map›Paper›PMID 42014683›Full record

ArticleCell death & disease2026

TGF-β/SMAD4/14-3-3σ/TFEB axis promotes mesenchymal-epithelial transition and inhibits autophagy in colorectal cancer.

Xiaoyan Chen, Markus Winter, Matjaz Rokavec, Janine König, Heiko Hermeking

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Review
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

5 authors.

Xiaoyan ChenExperimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-University München, Thalkirchner Strasse 36, D-80337, Munich, Germany.
Markus WinterExperimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-University München, Thalkirchner Strasse 36, D-80337, Munich, Germany.
Matjaz RokavecExperimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-University München, Thalkirchner Strasse 36, D-80337, Munich, Germany.ORCID http://orcid.org/0000-0002-2540-877X
Janine KönigExperimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-University München, Thalkirchner Strasse 36, D-80337, Munich, Germany.
Heiko HermekingExperimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-University München, Thalkirchner Strasse 36, D-80337, Munich, Germany. heiko.hermeking@med.uni-muenchen.de.ORCID http://orcid.org/0000-0001-6586-4406

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

14-3-3σ is a p53-inducible gene with tumor suppressive properties and SMAD4 is a transcription factor encoded by a tumor suppressor gene, which is commonly inactivated in colorectal cancer (CRC). Here, 14-3-3σ was characterized as direct transcriptional target of SMAD4. TGF-β treatment of tumoroids derived from CRC patients and mouse models resulted in a SMAD4-dependent induction of 14-3-3σ. In murine, intestinal epithelia, the apical expression of 14-3-3σ was dependent on Smad4. Ectopic SMAD4 or 14-3-3σ promoted mesenchymal-to-epithelial transition (MET) and suppressed invasion, migration, and autophagy of CRC cells. As experimental inactivation of 14-3-3σ abolished these tumor-suppressive functions of SMAD4, 14-3-3σ mediates these effects of SMAD4. Inhibition of autophagy and promotion of MET by SMAD4 was mediated by inhibition of TFEB via binding and sequestration of TFEB by 14-3-3σ. The association of 14-3-3σ and TFEB was dependent on phosphorylation of the TFEB serine 211 residue, which is a target of mTORC1. Taken together, the TGF-β/SMAD4/14-3-3σ/TFEB axes characterized here antagonizes epithelial plasticity and autophagy. Thereby, it may ultimately suppress the progression of CRC and other types of cancer.

Indexed as

14-3-3 ProteinsAutophagyBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsColorectal NeoplasmsEpithelial-Mesenchymal TransitionSmad4 ProteinTransforming Growth Factor betaAnimalsCell Line, TumorCell MovementExoribonucleasesHumansMicePhosphorylationSignal Transduction14-3-3 ProteinsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsExoribonucleasesSFN protein, humanSmad4 ProteinSMAD4 protein, humanTransforming Growth Factor beta

Identifiers

PMID42014683
PMCPMC13100165

What Socratic holds

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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 Socratic graph.