ArticleMolecular human reproduction2015
Epidermal growth factor-like domain 7 promotes migration and invasion of human trophoblast cells through activation of MAPK, PI3K and NOTCH signaling pathways.
Article in Molecular human reproduction, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Late-Onset Preeclampsia Is Linked to Extensive Remodeling of the Placental Extracellular Matrix.Medical sciences (Basel, Switzerland) · 2026Observational
- Effect of Pravastatin on Placental Expression of Epidermal Growth Factor-like Domain 7 in Early-Onset Pre-Eclampsia: A New Potential Mechanism of Action.Biomedicines · 2024Article
- Low EGFL7 expression is associated with high lymph node spread and invasion of lymphatic vessels in colorectal cancer.Scientific reports · 2023Article
- IFITM1 inhibits trophoblast invasion and is induced in placentas associated with IFN-mediated pregnancy diseases.iScience · 2023Article
- Evaluation Of Epidermal Growth Factor-Like Domain (EGFL7) mRNA Expression and its Protein Level in Preeclampsia.Journal of obstetrics and gynaecology of India · 2023Article
- Aspirin Inhibits Fibronectin Expression and Reverses Fibronectin-Mediated Cell Invasiveness by Activating Akt Signaling in Preeclampsia.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Placental Dysfunction in Assisted Reproductive Pregnancies: Perinatal, Neonatal and Adult Life Outcomes.International journal of molecular sciences · 2022Review
- A High-Throughput Toxicity Screen of 42 Per- and Polyfluoroalkyl Substances (PFAS) and Functional Assessment of Migration and Gene Expression in Human Placental Trophoblast Cells.Frontiers in toxicology · 2022Article
- Circulating EGFL7 distinguishes between IUGR and PE: an observational case-control study.Scientific reports · 2021Observational
- An increase in elastogenic components in the placental villi of women with chronic venous disease during pregnancy is associated with decreased EGFL7 expression level.Molecular medicine reports · 2021Observational
- Delta-like canonical Notch ligand 3 as a potential therapeutic target in malignancies: A brief overview.Cancer science · 2021Review
- Effect of Different Concentrations of Leukemia Inhibitory Factor on Gene Expression of Vascular Endothelial Growth Factor-A in Trophoblast Tumor Cell Line.International journal of fertility & sterility · 2020Article
- Exosomes as Messengers Between Mother and Fetus in Pregnancy.International journal of molecular sciences · 2020Review
- Placental DNA methylation changes associated with maternal prepregnancy BMI and gestational weight gain.International journal of obesity (2005) · 2020Article
- Molecular Signaling Regulating Endometrium-Blastocyst Crosstalk.International journal of molecular sciences · 2019Review
- Increased circulating levels of Epidermal Growth Factor-like Domain 7 in pregnant women affected by preeclampsia.Translational research : the journal of laboratory and clinical medicine · 2019Article
- A positive feed-forward loop between LncRNA-URRCC and EGFL7/P-AKT/FOXO3 signaling promotes proliferation and metastasis of clear cell renal cell carcinoma.Molecular cancer · 2019Article
- Attenuation of EGFL7 Expression Inhibits Growth Hormone-Producing Pituitary Adenomas Growth and Invasion.Human gene therapy · 2018Article
- Copper Nanoparticles Show ObviousInternational journal of biological sciences · 2018Article
- Transgenic Expression of A Venous Malformation Related Mutation,International journal of medical sciences · 2018Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Epidermal growth factor-like domain 7 (Egfl7) is a gene that encodes a partially secreted protein and whose expression is largely restricted to the endothelia. We recently reported that EGFL7 is also expressed by trophoblast cells in mouse and human placentas. Here, we investigated the molecular pathways that are regulated by EGFL7 in trophoblast cells. Stable EGFL7 overexpression in a Jeg3 human choriocarcinoma cell line resulted in significantly increased cell migration and invasiveness, while cell proliferation was unaffected. Analysis of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways showed that EGFL7 promotes Jeg3 cell motility by activating both pathways. We show that EGFL7 activates the epidermal growth factor receptor (EGFR) in Jeg3 cells, resulting in downstream activation of extracellular regulated kinases (ERKs). In addition, we provide evidence that EGFL7-triggered migration of Jeg3 cells involves activation of NOTCH signaling. EGFL7 and NOTCH1 are co-expressed in Jeg3 cells, and blocking of NOTCH activation abrogates enhanced migration of Jeg3 cells overexpressing EGFL7. We also demonstrate that signaling through EGFR and NOTCH converged to mediate EGFL7 effects. Reduction of endogenous EGFL7 expression in Jeg3 cells significantly decreased cell migration. We further confirmed that EGFL7 stimulates cell migration by using primary human first trimester trophoblast (PTB) cells overexpressing EGFL7. In conclusion, our data suggest that in trophoblast cells, EGFL7 regulates cell migration and invasion by activating multiple signaling pathways. Our results provide a possible explanation for the correlation between reduced expression of EGFL7 and inadequate trophoblast invasion observed in placentopathies.
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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.