Evidence map›Paper›PMID 41963301›Full record

ArticleCell death & disease2026

A FoxM1/Smad4 positive feedback loop promotes pancreatic cancer progression.

Banzhan Ruan, Bingshu Wang, Xiaodian Zhang, Fujin Liu, Zhenling Wan, Yan Chen, Julan Wu, Chun Luo, Wenyan Lu, Yanda Lu and 1 more

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. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Banzhan Ruan *Key Laboratory of Emergency and Trauma of Ministry of Education, Engineering Research Center for Hainan Biological Sample Resources of Major Diseases, Hainan Branch of National Clinical Research Center for Cancer, the First Affiliated Hospital, Hainan Medical University, Haikou, China.
Bingshu Wang *Key Laboratory of Emergency and Trauma of Ministry of Education, Engineering Research Center for Hainan Biological Sample Resources of Major Diseases, Hainan Branch of National Clinical Research Center for Cancer, the First Affiliated Hospital, Hainan Medical University, Haikou, China.
Xiaodian Zhang *Key Laboratory of Emergency and Trauma of Ministry of Education, Engineering Research Center for Hainan Biological Sample Resources of Major Diseases, Hainan Branch of National Clinical Research Center for Cancer, the First Affiliated Hospital, Hainan Medical University, Haikou, China.
Fujin Liu *Department of Pathology, Hainan General Hospital, Hainan Medical University, Haikou, China.
Zhenling WanDepartment of Pathology, Hainan Women and Children's Medical Center, Hainan Medical University, Haikou, China.
Yan ChenKey Laboratory of Emergency and Trauma of Ministry of Education, Engineering Research Center for Hainan Biological Sample Resources of Major Diseases, Hainan Branch of National Clinical Research Center for Cancer, the First Affiliated Hospital, Hainan Medical University, Haikou, China.
Julan WuDepartment of Pathology, Hainan General Hospital, Hainan Medical University, Haikou, China.
Chun LuoDepartment of Pathology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China.
Wenyan LuKey Laboratory of Emergency and Trauma of Ministry of Education, Engineering Research Center for Hainan Biological Sample Resources of Major Diseases, Hainan Branch of National Clinical Research Center for Cancer, the First Affiliated Hospital, Hainan Medical University, Haikou, China.
Yanda LuKey Laboratory of Emergency and Trauma of Ministry of Education, Engineering Research Center for Hainan Biological Sample Resources of Major Diseases, Hainan Branch of National Clinical Research Center for Cancer, the First Affiliated Hospital, Hainan Medical University, Haikou, China. luyandajx@sina.com.ORCID http://orcid.org/0000-0002-6595-1259
Shaojiang ZhengKey Laboratory of Emergency and Trauma of Ministry of Education, Engineering Research Center for Hainan Biological Sample Resources of Major Diseases, Hainan Branch of National Clinical Research Center for Cancer, the First Affiliated Hospital, Hainan Medical University, Haikou, China. zshaojiang@muhn.edu.cn.

Funding

Hainan Medical University (HMU) XRC200012Hainan Provincial Department of Science and Technology (Department of Science and Technology of Hainan Province) QCXM202017Hainan Provincial Department of Science and Technology (Department of Science and Technology of Hainan Province) ZDKJ2021038Hainan Provincial Department of Science and Technology (Department of Science and Technology of Hainan Province) ZDKJ2021038, ZDYF2026SHFZ039National Natural Science Foundation of China (National Science Foundation of China) 81960528, 82560493Natural Science Foundation of Hainan Province 820RC639
6 · The paper itself

Abstract

Pancreatic cancer is a highly lethal disease characterized by rapid onset, aggressive progression, and limited treatment options. The involvement of FoxM1 in the TGF-β/Smad signaling pathway has been linked to pancreatic cancer progression; however, the mechanisms behind the cooperative regulation of TGF-β signaling by FoxM1 and Smad4 remain poorly understood. In this study, we utilized molecular cytology techniques, animal models, and human pancreatic cancer tissues to investigate the role of FoxM1 in Smad4 stabilization and its regulation of TGF-β signaling. Our findings reveal that FoxM1 inhibits ubiquitin-proteasome-mediated degradation of Smad4, resulting in its stabilization. Once translocated into the nucleus, Smad4 binds to the FoxM1 promoter region, inducing FoxM1 expression and forming a positive feedback loop. Furthermore, we observed significantly higher expression of this feedback loop in pancreatic cancer tissues compared to adjacent normal tissues, with markedly elevated levels in poorly differentiated tissues compared to well-differentiated ones. Therefore, the loop aberrantly activates the TGF-β pathway, driving pancreatic cancer progression. These findings uncover a novel mechanism of TGF-β pathway activation and provide potential new targets for the prevention and treatment of pancreatic cancer. This study elucidates that FoxM1 functions to impede the ubiquitin proteasome-mediated degradation of Smad4, consequently stabilizing it. Following nuclear translocation, Smad4 binds to the FoxM1 promoter region, initiating FoxM1 expression and establishing a positive feedback loop. This loop plays a pivotal role in promoting pancreatic cancer development and migration by aberrantly activating the TGF-β pathway.

Indexed as

Forkhead Box Protein M1Pancreatic NeoplasmsSmad4 ProteinAnimalsCell Line, TumorDisease ProgressionFeedback, PhysiologicalGene Expression Regulation, NeoplasticHumansMiceMice, NudePromoter Regions, GeneticProteasome Endopeptidase ComplexSignal TransductionTransforming Growth Factor betaForkhead Box Protein M1FOXM1 protein, humanProteasome Endopeptidase ComplexSmad4 ProteinSMAD4 protein, humanTransforming Growth Factor beta

Identifiers

PMID41963301
PMCPMC13181101

What Socratic holds

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LicenceCC BY
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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.