Evidence map›Paper›PMID 40993484›Full record

ArticleMolecular and cellular biochemistry2026

FKH domain-mediated nuclear FOXP3 suppresses gastric cancer malignancy via c-MYC/CDKN1A regulation, EMT inhibition, and PI3K/AKT signaling modulation.

Yu Chen, Xia Zhao, Yuze Zhu, Ling Xu, Juanjuan Wang, Zheyi Chen, Hui Chen, Tingting Rong, Yanhui Ma, Yi Liu and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular and cellular biochemistry, 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. 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

14 authors.

Yu ChenSchool of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China.
Xia ZhaoDepartment of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuze ZhuCollege of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ling XuDepartment of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Juanjuan WangDepartment of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zheyi ChenDepartment of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hui ChenDepartment of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Tingting RongDepartment of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yanhui MaDepartment of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yi LiuDepartment of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yunlan ZhouDepartment of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yingxia ZhengDepartment of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. combi3230@163.com.
Lisong ShenSchool of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China. lisongshen@hotmail.com.
Guohua XieDepartment of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. xieguohua@xinhuamed.com.cn.

Funding

National Natural Science Foundation of China 81101848National Natural Science Foundation of China 81672363National Natural Science Foundation of China 82371738Shanghai Municipal Health Commission of Outstanding Youth Talent Program 20224Z0025Shanghai Natural Science Foundation 23ZR1441700
6 · The paper itself

Abstract

Gastric cancer (GC) remains a primary contributor to cancer-associated deaths worldwide, especially in East Asia. We investigated the function of nuclear-localized full-length FOXP3 (FOXP3FL) as an oncosuppressive factor in GC. Total FOXP3 was markedly reduced in GC tissues versus adjacent normal mucosa, with distinct cytoplasmic and nuclear patterns. Functional assays revealed that nuclear overexpression of FOXP3FL suppresses proliferation, migration, and invasion of GC cells in vitro and in vivo and promotes cellular senescence in vivo. Mechanistically, FOXP3FL directly represses MYC transcription and induces CDKN1A, thereby restraining proliferation and metastasis. These transcriptional changes, together with concomitant PTEN upregulation and PI3K-P110α downregulation, collectively attenuate PI3K/AKT signaling and impair epithelial-mesenchymal transition (EMT) in FOXP3FL-expressing GC cells. The forkhead (FKH) domain is essential: its deletion yields cytoplasmic FOXP3ΔFKH, which loses transcriptional control and antitumor activity. Our findings underscore nuclear-localized FOXP3FL as a tumor suppressor whose FKH domain is integral to its suppressive function.

Indexed as

Cell NucleusCyclin-Dependent Kinase Inhibitor p21Epithelial-Mesenchymal TransitionForkhead Transcription FactorsGene Expression Regulation, NeoplasticNeoplasm ProteinsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mycSignal TransductionStomach NeoplasmsAnimalsCell Line, TumorCell ProliferationHumansMiceCDKN1A protein, humanCyclin-Dependent Kinase Inhibitor p21Forkhead Transcription FactorsFOXP3 protein, humanMYC protein, humanNeoplasm ProteinsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mycc-MYC/CDKN1AEMTFOXP3FLFOXP3ΔFKHGastric cancerPI3K/AKT

Identifiers

PMID40993484

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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 OpenQuestion graph.