Evidence map›Paper›PMID 34620174›Full record

ArticleCell communication and signaling : CCS2021

EGF stimulates human trophoblast cell invasion by downregulating ID3-mediated KISS1 expression.

Lanlan Fang, Yibo Gao, Zhen Wang, Yuxi Li, Yang Yan, Ze Wu, Jung-Chien Cheng, Ying-Pu Sun

Open access · goldAbstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
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

24 citing papers in PubMed, 29 citations in OpenAlex.

  1. Trial
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  7. Epidermal growth factor receptor in placental health and disease: pathways, dysfunction, and chemical disruption.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Review
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  18. Evolutionary divergence of embryo implantation in primates.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022
    Review
  19. Article
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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 at 2 institutions in 1 country.

Lanlan Fang *Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 40, Daxue Road, Zhengzhou, 450052, Henan, China.
Yibo Gao *Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 40, Daxue Road, Zhengzhou, 450052, Henan, China.
Zhen WangCenter for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 40, Daxue Road, Zhengzhou, 450052, Henan, China.
Yuxi LiCenter for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 40, Daxue Road, Zhengzhou, 450052, Henan, China.
Yang YanCenter for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 40, Daxue Road, Zhengzhou, 450052, Henan, China.
Ze WuCenter for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 40, Daxue Road, Zhengzhou, 450052, Henan, China.
Jung-Chien ChengCenter for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 40, Daxue Road, Zhengzhou, 450052, Henan, China. jungchien.cheng@gmail.com.ORCID 0000-0002-5399-9327
Ying-Pu SunCenter for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 40, Daxue Road, Zhengzhou, 450052, Henan, China. syp2008@vip.sina.com.
First Affiliated Hospital of Zhengzhou University · CNFirst Affiliated Hospital of Henan University · CN

Funding

henan province medical science and technique r&d program SBGJ202002046henan province medical science and technique r&d program SBGJ202002052key r&d program of henan province 202102310062national natural science foundation of china 2019YFA 0110900national natural science foundation of china 32050410302national natural science foundation of china 32070848national natural science foundation of china 81820108016special fund for young teachers from the zhengzhou university JC202054006
6 · The paper itself

Abstract

backgroundDuring pregnancy, trophoblast cell invasion needs to be finely controlled. Aberrant trophoblast cell invasion is associated with placental diseases. Epidermal growth factor (EGF) and its receptor, EGFR, are expressed in trophoblast cells. Although the pro-invasive effect of EGF on trophoblast cells has been reported, the underlying mechanism remains largely unknown.

resultsIn the present study, we conducted an RNA sequencing (RNA-seq) to HTR-8/SVneo human trophoblast cells in response to EGF and identified KISS1 as a target gene of EGF. The human KISS1 gene encodes kisspeptin, also known as metastin, which can suppress tumor metastasis. Our results showed that EGF treatment downregulated KISS1 expression and secretion by activating the EGFR-mediated PI3K/AKT signaling pathway. In addition, the expression of inhibitor of DNA-binding protein 3 (ID3) was downregulated by EGF and that was required for the EGF-suppressed KISS1 expression. Functionally, transwell invasion assays demonstrated that EGF stimulated human trophoblast cell invasion by downregulating KISS1 expression. Preeclampsia (PE) is a placental disease characterized by insufficient trophoblast cell invasion. Our clinical results revealed that serum levels of EGF were downregulated while serum and placental levels of KISS1 were upregulated in PE patients.

conclusionsThis study demonstrates that downregulation of EGF can lead to poor trophoblast cell invasion by increasing KISS1 expression which subsequently contributes to the pathogenesis of PE. Video Abstract.

Indexed as

Cell MovementEpidermal Growth FactorErbB ReceptorsFemaleHumansInhibitor of Differentiation ProteinsKisspeptinsNeoplasm InvasivenessNeoplasm MetastasisNeoplasm ProteinsPhosphatidylinositol 3-KinasesPlacentaPlacenta DiseasesPre-EclampsiaPregnancyProto-Oncogene Proteins c-aktEGFR protein, humanEpidermal Growth FactorErbB ReceptorsID3 protein, humanInhibitor of Differentiation ProteinsKISS1 protein, humanKisspeptinsNeoplasm ProteinsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktEGFID3KISS1PreeclampsiaTrophoblast invasion

Identifiers

PMID34620174
PMCPMC8499481
OpenAlexW3203273519

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.