Evidence map›Paper›PMID 41398593›Full record

ArticleBiology direct2025

Platelet-activating factor induces ferroptosis by binding to ATF3 and inhibiting the SLC7A11/GPX4 axis to suppress the progression of endometrial carcinoma.

Feifei Pan, Yuqing Qiu, Zhuojie Huang, Yanqin Zheng, Yun Chen, Yiming Song, Zhe-Sheng Chen, Lirong Guo, Jingyao Wang, Xiaojie Liu and 5 more

Abstract read
In one paragraph

Article in Biology direct, 2025. 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

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

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

15 authors.

Feifei PanDepartment of Gynecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China.
Yuqing QiuDepartment of Gynecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China.
Zhuojie HuangDepartment of Pediatrics, Guangzhou Medical University, Guangzhou, 511436, China.
Yanqin ZhengDepartment of Gynecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China.
Yun ChenDepartment of Gynecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China.
Yiming SongDepartment of Gynecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China.
Zhe-Sheng ChenDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, New York, 11439, USA.
Lirong GuoDepartment of Gynecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China.
Jingyao WangDepartment of Gynecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China.
Xiaojie LiuInstitute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
Zixin TaoDepartment of Gynecology and Obstetrics, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, 510180, China.
Yaqiong LiuDepartment of Gynecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China.
Xingcui XuanDepartment of Gynecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China.
Kunxiang GongDepartment of Pathology, First School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, Guangzhou, Guangdong, 510080, China. gkx13265040169@126.com.
Kun ShiDepartment of Gynecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China. shikun28@hotmail.com.

Funding

Basic and Applied Basic Research Foundation of Guangdong Province 2022A1515220127Basic and Applied Basic Research Foundation of Guangdong Province 2025A1515011310National Natural Science Foundation of China 82072859National Natural Science Foundation of China 82404926
6 · The paper itself

Abstract

backgroundEndometrial carcinoma (EC) is an aggressive gynecological malignancy with high recurrence rates and limited treatment options. Patients with EC exhibit elevated serum levels of lyso-platelet-activating factor (lyso-PAF), a biologically inactive product generated during the hydrolysis of PAF by PAF-acetylhydrolase (II) (PAF-AH2). Nevertheless, the biological function of PAF in EC progression and the relationship between abnormal lyso-PAF levels and EC progression remain unclear.

resultsIn this study, we identified the bioactive phospholipid mediator–PAF, which effectively suppress tumor growth both in vitro and in patient-derived organoid models. By combining the cellular thermal shift assay, drug affinity responsive target stability approach, molecular docking simulation, and surface plasmon resonance analysis, we identified activating transcription factor 3 (ATF3) as the direct binding target of PAF with a Kd of 3 0.24 µM. Mechanistically, PAF enhanced ATF3 stability through deubiquitination. In addition, ATF3 knockdown partially reversed the effects of PAF-induced SLC7A11 and GPX4 transcriptional inhibition. In vivo studies using a nude mouse xenograft model confirmed the ferroptosis-mediated tumor-suppressive effects of PAF, as evidenced by hematoxylin and eosin staining and immunohistochemical analysis. Clinically, proteomic analysis revealed upregulation of PAF-AH2 expression in EC tissues derived from patients. Subsequent analysis of EC tissue microarrays revealed that high PAF-AH2 expression is associated with poor survival.

conclusionsIn conclusion, this study demonstrates that PAF inhibits EC tumor growth by inducing ferroptosis and that the underlying mechanisms of its action involve the targeting of ATF3. These findings suggest that PAF metabolism may be a promising direction for EC diagnostics and therapeutics.

Indexed as

Activating Transcription Factor 3Endometrial NeoplasmsFerroptosisPlatelet Activating FactorAnimalsCell Line, TumorDisease ProgressionFemaleHumansMiceMice, NudeActivating Transcription Factor 3ATF3 protein, humanPlatelet Activating FactorATF3Endometrial carcinomaFerroptosisPAF-AH2Platelet-activating factor

Identifiers

PMID41398593
PMCPMC12805724

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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.