Evidence map›Paper›PMID 41972409›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

DTX3L Inhibits the EMT, Metastasis, and Stem-Like Features of Gastric Cancer Through Promoting GSK-3β Dependent SNAI1 Decay.

Yang Chen, Zhen Li, Jiajia Shen, Jingyu Lin, Xiaoli Zhao, Rui Zhang, Ying Han, Zhen Wang

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

8 authors.

Yang ChenDepartment of Biochemistry, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0009-0005-2794-2780
Zhen LiDepartment of Biochemistry, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0009-0007-9434-7214
Jiajia ShenDepartment of Biochemistry, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0009-0006-4260-7603
Jingyu LinDepartment of Biochemistry, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0009-0008-3259-5498
Xiaoli ZhaoDepartment of Biochemistry, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0000-0002-2838-7687
Rui ZhangDepartment of Biochemistry, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0009-0002-9023-2624
Ying HanDepartment of Biochemistry, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0000-0003-0379-7433
Zhen WangDepartment of Biochemistry, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0000-0002-6377-3890

Funding

CAMS Innovation Fund for Medical Sciences 2025-2025I2MKJ019National Natural Science Foundation of China 82473100
6 · The paper itself

Abstract

Gastric cancer remains a leading cause of cancer mortality worldwide, largely due to its high metastatic potential driven by epithelial-mesenchymal transition (EMT). Here, we identify Deltex E3 ubiquitin ligase 3L (DTX3L) as a previously unrecognized tumor suppressor in gastric cancer. DTX3L expression is markedly reduced in metastatic and mesenchymal-type gastric cancers and positively correlates with favorable patient prognosis. Functional analyses in cell lines, organoids and animal models demonstrate that DTX3L depletion promotes gastric cancer cell migration, invasion, stem-like properties and metastasis, whereas its overexpression exhibits opposite effects. Mechanistically, DTX3L acts as an E3 ubiquitin ligase that directly interacts with and ubiquitinates SNAI1, a master EMT regulator, leading to its GSK-3β dependent proteasomal degradation. Loss of DTX3L stabilizes SNAI1 and enhances EMT and stem-like phenotypes. Moreover, we uncover that TGF-β1-induced miR-135b-5p downregulates DTX3L, forming a regulatory axis that promotes EMT. Collectively, our findings reveal a novel DTX3L-SNAI1 signaling pathway governing EMT and metastasis in gastric cancer, providing mechanistic insight and suggesting DTX3L as a potential prognostic biomarker and therapeutic target.

Indexed as

Epithelial-Mesenchymal TransitionGlycogen Synthase Kinase 3 betaSnail Family Transcription FactorsStomach NeoplasmsUbiquitin-Protein LigasesAnimalsCell Line, TumorCell MovementGene Expression Regulation, NeoplasticHumansMiceNeoplasm MetastasisNeoplastic Stem CellsGlycogen Synthase Kinase 3 betaSNAI1 protein, humanSnail Family Transcription FactorsUbiquitin-Protein LigasesDTX3LEMTgastric cancerSNAI1ubiquitination

Identifiers

PMID41972409
PMCPMC13334627

What OpenQuestion holds

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LicenceCC BY
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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.