Evidence map›Paper›PMID 41664169›Full record

ArticleGenome biology2026

Ubiquitination degradation of GATA4 by CUL4B promotes ovarian cancer metastasis by inducing lysosomal acidification.

Xin Yin, Rufei Gao, Yanqing Geng, Xinyi Mu, Yan Zhang, Yidan Ma, Xuemei Chen, Fei Han, Zhuxiu Chen, Fangfang Li and 1 more

Abstract read
In one paragraph

Article in Genome biology, 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

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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

11 authors.

Xin YinJoint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, 400016, PR China. yinxin@cqmu.edu.cn.
Rufei GaoJoint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, 400016, PR China.
Yanqing GengJoint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, 400016, PR China.
Xinyi MuJoint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, 400016, PR China.
Yan ZhangJoint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, 400016, PR China.
Yidan MaJoint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, 400016, PR China.
Xuemei ChenJoint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, 400016, PR China.
Fei HanJoint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, 400016, PR China.
Zhuxiu ChenJoint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, 400016, PR China.
Fangfang LiJoint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, 400016, PR China.
Junlin HeJoint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, 400016, PR China. hejunlin@cqmu.edu.cn.

Funding

Special Funding for Postdoctoral Research Project of Chongqing CSTB2023NSCQ-BHX0024the National Natural Science Foundation of China 82303095the Special Professorship Project of Chongqing Medical 2021-215
6 · The paper itself

Abstract

backgroundOvarian cancer remains highly lethal due to late-stage diagnosis and aggressive metastatic potential. Lysosomal acidification plays a critical role in tumor metastasis, regulated by multiple genetic factors. While GATA4 is a well-established transcriptional activator in cardiomyogenesis, its function in carcinogenesis remains ambiguous, particularly in ovarian cancer, and its impact on lysosomal regulation is poorly understood. Therefore, we aim to elucidate the function of GATA4 in ovarian cancer metastasis and the underlying molecular mechanisms.

resultsWe find that downregulation of GATA4 in ovarian cancer correlates with enhanced lysosomal acidification, increased cell proliferation, and elevated lung and abdominal metastasis both in vitro and in vivo. Mechanistically, GATA4 interacts with the CRL4B complex and undergoes CUL4B-mediated ubiquitination at lysine residues 329 and 404. Integrated RNA-seq and CUT&Tag, ChIP-qPCR, and dual-luciferase assays reveal that GATA4 activates H3K27ac modification at tumor suppressor gene TRIM22, consequently modulating epithelial-mesenchymal transition and lysosomal acidification. These findings demonstrate that GATA4 suppresses lysosomal acidification and epithelial-mesenchymal transition, while its CRL4B-mediated ubiquitination and degradation in metastatic ovarian cancer cells leads to reduced H3K27ac modification at tumor suppressor genes.

conclusionsOur study elucidates the tumor-suppressive role of GATA4 in regulating lysosomal acidification and epithelial-mesenchymal transition through ubiquitination-dependent mechanisms and histone acetylation modulation. The findings identify GATA4 as a promising therapeutic target and diagnostic marker for ovarian cancer intervention.

Indexed as

Cullin ProteinsGATA4 Transcription FactorLysosomesOvarian NeoplasmsUbiquitinationAnimalsCell Line, TumorCell ProliferationEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHumansMiceNeoplasm MetastasisProteolysisCullin ProteinsGATA4 protein, humanGATA4 Transcription FactorCUL4BEpithelial–mesenchymal transitionGATA4H3K27acLysosomal acidificationOvarian cancerUbiquitination

Identifiers

PMID41664169
PMCPMC12983490

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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 OpenQuestion graph.