ArticleCell death and differentiation2015
ADAM12-directed ectodomain shedding of E-cadherin potentiates trophoblast fusion.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 70 citations in OpenAlex.
- Spatio-temporal expression of E-cadherin mediates trophoblast lineage transitions during human placentation.Molecular biology reports · 2026Review
- ADAM20 Participates Modestly to Fertilization as Its Absence Leads to In Vitro Hypofertility in Mouse.Cell biochemistry and function · 2026Article
- DHODH regulates trophoblast fusion via IFITM-reduced plasma membrane fluidity: Implications for hypertensive disorders of pregnancy.iScience · 2026Article
- Advantages, limitations, and innovative considerations for established and emerging models of human placental syncytiotrophoblast.Human reproduction update · 2026Review
- Glycolytic reprogramming mediated by the ADAM12/IGF1 axis promotes ossification of the posterior longitudinal ligament.Cell death discovery · 2026Article
- Trophoblast Fusion Deficiency in Placenta-Related Pregnancy Disorders.Advances in experimental medicine and biology · 2026Review
- Understanding the involvement of HtrA4 during syncytiotrophoblast differentiation.Frontiers in cell and developmental biology · 2026Article
- Implications of Heterotypic Cell Fusion in Cancer.Advances in experimental medicine and biology · 2026Review
- Molecular profiles of the great obstetrical syndromes reveal common features and dynamic changes in early pregnancy.Communications medicine · 2025Article
- Article
- Placental cytotrophoblast microvillar stabilization is required for cell-cell fusion.Development (Cambridge, England) · 2025Article
- Role of E-cadherin in epithelial barrier dysfunction: implications for bacterial infection, inflammation, and disease pathogenesis.Frontiers in cellular and infection microbiology · 2025Review
- Epigenetic drug screening for trophoblast syncytialization reveals a novel role for MLL1 in regulating fetoplacental growth.BMC medicine · 2024Article
- Single-nucleus multi-omic profiling of human placental syncytiotrophoblasts identifies cellular trajectories during pregnancy.Nature genetics · 2024Article
- Mechanisms of Cell Fusion in Cancer.Results and problems in cell differentiation · 2024Review
- A comprehensive review of human trophoblast fusion models: recent developments and challenges.Cell death discovery · 2023Review
- ADAM12 promotes gemcitabine resistance by activating EGFR signaling pathway and induces EMT in bladder cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- SLC20a1/PiT-1 is required for chorioallantoic placental morphogenesis.Vascular biology (Bristol, England) · 2023Article
- Modulation of the E-cadherin in human cells infected in vitro with Coxiella burnetii.PloS one · 2023Article
- Extracellular Events Involved in Cancer Cell-Cell Fusion.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trophoblasts, placental cells of epithelial lineage, undergo extensive differentiation to form the cellular components of the placenta. Trophoblast progenitor cell differentiation into the multinucleated syncytiotrophoblast is a key developmental process required for placental function, where defects in syncytiotrophoblast formation and turnover associate with placental pathologies and link to poor pregnancy outcomes. The cellular and molecular processes governing syncytiotrophoblast formation are poorly understood, but require the activation of pathways that direct cell fusion. The protease, A Disintegrin and Metalloproteinase 12 (ADAM12), controls cell fusion in myoblasts and is highly expressed in the placenta localizing to multiple trophoblast populations. However, the importance of ADAM12 in regulating trophoblast fusion is unknown. Here, we describe a function for ADAM12 in regulating trophoblast fusion. Using two distinct trophoblast models of cell fusion, we show that ADAM12 is dynamically upregulated and is under the transcriptional control of protein kinase A. siRNA-directed loss of ADAM12 impedes spontaneous fusion of primary cytotrophoblasts, whereas overexpression of the secreted variant, ADAM12S, potentiates cell fusion in the Bewo trophoblast cell line. Mechanistically, both ectopic and endogenous levels of ADAM12 were shown to control trophoblast fusion through E-cadherin ectodomain shedding and remodeling of intercellular boundaries. This study describes a novel role for ADAM12 in placental development, specifically highlighting its importance in controlling the differentiation of villous cytotrophoblasts into multinucleated cellular structures. Moreover, this work identifies E-cadherin as a novel ADAM12 substrate, and highlights the significance that cell adhesion molecule ectodomain shedding has in normal development.
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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.